Publications by authors named "Francisca Sousa"

139 Publications

A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure.

Am J Gastroenterol 2021 Sep 9. Epub 2021 Sep 9.

Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Spain.

Introduction: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR.

Methods: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months).

Results: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007).

Discussion: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.
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http://dx.doi.org/10.14309/ajg.0000000000001503DOI Listing
September 2021

Involvement of anti-inflammatory, antioxidant, and BDNF up-regulating properties in the antipsychotic-like effect of the essential oil of Alpinia zerumbet in mice: a comparative study with olanzapine.

Metab Brain Dis 2021 Dec 7;36(8):2283-2297. Epub 2021 Sep 7.

Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo, 1000, 60431-270, Fortaleza, CE, Brazil.

The current drug therapy for schizophrenia effectively treats acute psychosis and its recurrence; however, this mental disorder's cognitive and negative symptoms are still poorly controlled. Antipsychotics present important side effects, such as weight gain and extrapyramidal effects. The essential oil of Alpinia zerumbet (EOAZ) leaves presents potential antipsychotic properties that need further preclinical investigation. Here, we determined EAOZ effects in preventing and reversing schizophrenia-like symptoms (positive, negative, and cognitive) induced by ketamine (KET) repeated administration in mice and putative neurobiological mechanisms related to this effect. We conducted the behavioral evaluations of prepulse inhibition of the startle reflex (PPI), social interaction, and working memory (Y-maze task), and verified antioxidant (GSH, nitrite levels), anti-inflammatory [interleukin (IL)-6], and neurotrophic [brain-derived neurotrophic factor (BDNF)] effects of this oil in hippocampal tissue. The atypical antipsychotic olanzapine (OLZ) was used as standard drug therapy. EOAZ, similarly to OLZ, prevented and reversed most KET-induced schizophrenia-like behavioral alterations, i.e., sensorimotor gating deficits and social impairment. EOAZ had a modest effect on the prevention of KET-associated working memory deficit. Compared to OLZ, EOAZ showed a more favorable side effects profile, inducing less cataleptic and weight gain changes. EOAZ efficiently protected the hippocampus against KET-induced oxidative imbalance, IL-6 increments, and BDNF impairment. In conclusion, our data add more mechanistic evidence for the anti-schizophrenia effects of EOAZ, based on its antioxidant, anti-inflammatory, and BDNF up-regulating actions. The absence of significant side effects observed in current antipsychotic drug therapy seems to be an essential benefit of the oil.
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http://dx.doi.org/10.1007/s11011-021-00821-5DOI Listing
December 2021

Mechanism of preservation of the intestinal mucosa architecture and NF-κB/PGE2 reduction by hydrogen sulfide on cholera toxin-induced diarrhea in mice.

Life Sci 2021 Nov 3;284:119869. Epub 2021 Aug 3.

Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Post-graduation Program in Biotechnology, Parnaiba Delta Federal University, Parnaíba, PI, Brazil; Northeast Biotechnology Network (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil. Electronic address:

Aims: Investigate the involvement of Hydrogen sulfide (HS) in inflammatory parameters and intestinal morphology caused by cholera toxin (CT) in mice.

Main Methods: Mice were subjected to the procedure of inducing diarrhea by CT in the isolated intestinal loop model. The intestinal loops were inoculated with HS donor molecules (NaHS and GYY 4137) or saline and CT. To study the role of EP2 and EP4 prostaglandin E2 (PGE2) receptors in the HS antisecretory effect, PAG (DL-propargylglycine - inhibitor of cystathionine-γ-lyase (CSE)), PF-04418948 (EP2 antagonist) and ONO-AE3-208 (EP4 antagonist) were used. The intestinal loops were evaluated for intestinal secretion, relation of the depth of villi and intestinal crypts, and real-time PCR for the mRNA of the CXCL2, IL-6, NOS-2, IL-17, NF-κB1, NF-κBIA, SLC6A4 and IFN-γ genes.

Key Findings: HS restored the villus/crypt depth ratio caused by CT. NaHS and GYY 4137 increased the expression of NF-κB1 and for the NF-κBIA gene, only GYY 4137 increased the expression of this gene. The increased expression of NF-κB inhibitors, NF-κB1 and NF-κBIA by HS indicates a possible decrease in NF-κB activity. The pretreatment with PAG reversed the protective effect of PF-04418948 and ONO-AE3-208, indicating that HS probably decreases PGE2 because in the presence of antagonists of this pathway, PAG promotes intestinal secretion.

Significance: Our results point to a protective activity of HS against CT for promoting a protection of villus and crypt intestine morphology and also that its mechanism occurs at least in part due to decreasing the activity of NF-κB and PGE2.
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http://dx.doi.org/10.1016/j.lfs.2021.119869DOI Listing
November 2021

Doxycycline at subantimicrobial dose combined with escitalopram reverses depressive-like behavior and neuroinflammatory hippocampal alterations in the lipopolysaccharide model of depression.

J Affect Disord 2021 09 5;292:733-745. Epub 2021 Jun 5.

Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil. Electronic address:

Doxycycline (DOXY) is a second-generation tetracycline with anti-inflammatory and neuroprotective effects. A proinflammatory profile seems to predict the severity of depressive symptoms. In the present study, we aimed at determining whether the anti-inflammatory action of subantimicrobial-dose doxycycline (SDD) (DOXY, 10mg/kg), alone or combined with the antidepressant escitalopram (ESC), could revert lipopolysaccharide-induced depressive-like alterations in mice. Male Swiss mice received saline or lipopolysaccharide (LPS) for ten consecutive days. From the 6 day of LPS exposure, they were treated with DOXY 10 mg/kg, ESC 4 mg/kg, DOXY 10 mg/kg plus ESC 4 mg/kg (DOXY+ESC), or saline. On the 10 day, we assessed behavioral despair (forced swimming test), anhedonia (sucrose preference test), brain oxidative stress markers, and inflammatory and protective pathways related to depression, such as NF-kB and phospho-CREB. Our results showed that DOXY alone or combined with ESC reduced hippocampal Iba-1 expression and interleukin (IL)-1β levels. Only DOXY+ESC successfully reversed the LPS-induced increase in NF-kBp65 expression and TNFα levels. DOXY caused a marked increase in the hippocampal expression of phospho-CREB and GSH concentrations. DOXY and DOXY+ESC showed a tendency to modulate the functional status of mitogen-activated kinase p42-44 (Phospho-p44/42 MAPK) and of the phosphorylated form of glycogen synthase kinase 3 beta (GSK3β), revealing a protective profile against inflammation. In conclusion, SDD, combined with ESC, seems to be a good strategy for reverting inflammatory changes and protecting against depression.
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http://dx.doi.org/10.1016/j.jad.2021.05.083DOI Listing
September 2021

Photodynamic Therapy With Propolis: Antibacterial Effects on and Escherichia coli Analysed by Atomic Force Microscopy.

J Lasers Med Sci 2020 30;11(Suppl 1):S107-S112. Epub 2020 Dec 30.

Medical Professor at the Faculty of Human, Exact and Health Sciences of Piauí of the Institute of Higher Education of Vale do Parnaíba, Parnaíba, PI, Brazil.

Photodynamic therapy (PDT) is a process that uses a light source (e.g. laser), oxygen molecules and a photosensitizing agent. PDT aims to act against pathogens, including those resistant to antimicrobials. The association of PDT with natural drugs, such as Propolis, has not been widely studied. Therefore, this study aimed to evaluate the antimicrobial effect of PDT in vitro by using Propolis as a photosensitizing agent. For this purpose, the dry Propolis extract was used as a photosensitizer and a low-power laser (Photon Laser III model) was irradiated onto the microwells for 90 seconds. Gram-positive and Gram-negative bacterial strains were used in the tests at a concentration of 5 × 10 CFU/mL. Initially, the antibacterial activity of the photosensitizers without laser action was determined by using a serial microdilution method before the experiment with a laser. After the incubation of the plates in a bacteriological oven, resazurin (0.1%) was added and the minimum inhibitory concentration (MIC) was determined. Alterations in the morphology of the bacteria were analysed by using atomic force microscopy (AFM). Bacteria were sensitive to Propolis with MICs ranging from 13.75 to 0.85 mg/mL, but no susceptibility was observed for methylene blue without laser application. A change was observed for MIC values of Propolis against after irradiation, which decreased from 1.71 mg/mL to 0.85 mg/mL. However, this behaviour was not observed in , the only gram-negative strain used. In addition, AFM images revealed alterations in the size of one of the bacteria tested. The Propolis is more active against gram-positive bacteria and PDT improved its activity against one of the strains tested.
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http://dx.doi.org/10.34172/jlms.2020.S17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956024PMC
December 2020

Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice.

Eur J Pharmacol 2021 Jul 24;902:174113. Epub 2021 Apr 24.

Biotechnology and Biodiversity Center Research (BIOTEC), Post-graduation Program in Biotechnology, Federal University of the Parnaíba Delta (UFDPar), Parnaíba, PI, Brazil; The Northeastern Biotechnology Network (RENORBIO), Federal University of Piauí (UFPI), Teresina, PI, Brazil. Electronic address:

The transient receptor potential vanilloid channel 4 (TRPV4) is associated with the development of several pathologies, particularly gastric disorders. However, there are no studies associating this receptor with the pathophysiology of gastric erosions. The aim of this study was to investigate the role of TRPV4 in the development of ethanol-induced gastric damage in vivo. Gastric lesions were induced by ethanol in Swiss mice pretreated with TRPV4 antagonists, GSK2193874 (0.1; 0.3 and 0.9 mg/kg) or Ruthenium red (0.03; 0.1 or 0.3 mg/kg) or its agonist, GSK1016790A (0.9 mg/kg). Gastric mucosal samples were taken for histopathology, immunohistochemistry, atomic force microscopy and evaluation of antioxidant parameters. The gastric mucus content and TRPV4 mRNA expression were analyzed. Ethanol exposure induced upregulation of gastric mRNA and protein expression of TRPV4. TRPV4 blockade promoted gastroprotection against ethanol-induced injury on macro- and microscopic levels, leading to reduced hemorrhage, cell loss and edema and enhanced gastric mucosal integrity. Moreover, an increase in superoxide dismutase (SOD) and glutathione (GSH) activity was observed, followed by a decrease in malondialdehyde (MDA) levels. TRPV4 blockade during alcohol challenge reestablished gastric mucus content. The combination of TRPV4 agonist and ethanol revealed macroscopic exacerbation of gastric damage area. Our results confirmed the association of TRPV4 with the development of gastric injury, showing the importance of this receptor for further investigations in the field of gastrointestinal pathophysiology and pharmacology.
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http://dx.doi.org/10.1016/j.ejphar.2021.174113DOI Listing
July 2021

Is Riparin III a promising drug in the treatment for depression?

Eur J Pharm Sci 2021 Jul 30;162:105824. Epub 2021 Mar 30.

Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

Stress is crucially related to the pathophysiology of mood disorders, including depression. Since the effectiveness and number of the current pharmacological options still presents significant limitations, research on new substances is paramount. In rodents, several findings have indicated that corticosterone administration induces the manifestation of behavioral and neurochemical aspects of depression. Recently, riparin III has shown antidepressant-like properties in trials performed on animal models. Thus, our goal was to investigate the effects of riparin III on behavioral tests, monoamines levels, oxidative stress and cytokines levels in chronic corticosterone-induced model of depression. To do this, female swiss mice were treated with subcutaneous administration of corticosterone for 22 days. In addition, for the last 10 days, riparin III or fluvoxamine were also administered per os in specific test groups. Control groups received subcutaneous saline injections or distilled water per os. At the end of the timeline, the animals were killed and their hippocampi, prefrontal cortex, and striatum dissected for neurochemical analysis. Brain changes following corticosterone administration were confirmed, and riparin III could reversed the most abnormal behavioral and neurochemical corticosterone-induced alterations. These results suggest the potential antioxidant, anti-inflammatory and antidepressant effects of riparin III after a chronic stress exposure.
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http://dx.doi.org/10.1016/j.ejps.2021.105824DOI Listing
July 2021

Anti-diarrheal therapeutic potential of diminazene aceturate stimulation of the ACE II/Ang-(1-7)/Mas receptor axis in mice: A trial study.

Biochem Pharmacol 2021 04 6;186:114500. Epub 2021 Mar 6.

The Northeast Biotechnology Network (RENORBIO), Federal University of Piauí, Teresina, PI 64049-550, Brazil; Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (Lafidg), Federal University of Parnaíba Delta (UFDPar), Av. São Sebastião, n° 2819, CEP 64202-02 Parnaíba, PI, Brazil; Biotechnology and Biodiversity Center Research, BIOTEC, Federal University of Parnaíba Delta, Parnaíba, PI 64202-020, Brazil.

The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1-7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1-7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na/K-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1-7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1-7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.
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http://dx.doi.org/10.1016/j.bcp.2021.114500DOI Listing
April 2021

Construction and validation of educational technology to prevent complications in intestinal ostomies / periestomy skin.

Rev Bras Enferm 2020 21;73(suppl 5):e20190825. Epub 2020 Dec 21.

Universidade Regional do Cariri. Crato, Ceará, Brazil.

Objective: To build and validate an educational booklet for preventing complications in intestinal ostomy and peristomy skin.

Methods: Methodological study developed in: 1. Survey of the clinical profile of patients; 2. Integrative review; 3. Construction of technology; 4. Validation of educational material. The Delphi technique was used, with 18 judges with expertise in the field of stomatherapy. For data treatment, the Collective Subject Discourse (CSD), descriptive analysis, Kappa Index (K), binomial test and Content Validity Index (CVI) were used.

Results: The agreement rate between judges was higher than 0.61, for K p> 0.05, a proportion of 80% for the binomial test and 80% for the CVI. . The booklet showed an excellent index for K, binomial test and global content validity, becoming validated.

Final Considerations: The booklet was validated in appearance and content, being an instrument that can favor communication between professionals and people with ostomies.
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http://dx.doi.org/10.1590/0034-7167-2019-0825DOI Listing
June 2021

First pregnancy after in vitro culture of early antral follicles in goats: Positive effects of anethole on follicle development and steroidogenesis.

Mol Reprod Dev 2020 09 6;87(9):966-977. Epub 2020 Aug 6.

Faculty of Veterinary Medicine, Laboratory of Manipulation of Oocytes and Preantral Follicles (Lamofopa), State University of Ceara, Fortaleza, Ceará, Brazil.

This study aimed to evaluate the role of anethole during the in vitro culture of caprine early antral follicles. Early antral follicles were isolated from caprine ovaries and cultured for 18 days without (control) or with anethole (300 µg/ml). After culture, the cumulus-oocyte complexes were subjected to in vitro maturation, followed by parthenogenetic activation or in vitro fertilization (IVF) and embryo culture. Follicular walls were used for the quantification of messenger RNA (mRNA) of CYP19A1, CYP17, MMP-9, TIMP-2, Bax, and Bcl-2 genes, and culture medium was used for evaluation of ferric reducing antioxidant power (FRAP) and estradiol levels. After in vitro follicle culture (IVFC), anethole induced higher total antioxidant capacity, that is, it produced higher FRAP levels, reduced the Bax/Bcl-2 ratio, and increased the levels of mRNA for CYP19A1 and CYP17, which was associated with a greater estradiol production (p < .05). Also, anethole improved the ability of oocytes to resume meiosis and reach metaphase II stage, as well as yielded higher (p < .05) embryo production (e.g., morulas and blastocysts) in both parthenogenetic activation and IVF techniques. One pregnancy (Day 30) was obtained from IVFC with anethole. In conclusion, anethole promoted in vitro growth and maturation of goat early antral follicles and oocytes and enabled embryo production. Furthermore, this study reports, for the first time in goats, a pregnancy after IVF using oocytes originated from early antral follicles grown in vitro.
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http://dx.doi.org/10.1002/mrd.23410DOI Listing
September 2020

A comprehensive review of therapeutic approaches available for the treatment of cholera.

J Pharm Pharmacol 2020 Dec 31;72(12):1715-1731. Epub 2020 Jul 31.

Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (Lafidg), Post-graduation Program in Biotechnology, Federal University of Parnaíba Delta, Parnaíba, Brazil.

Objectives: The oral rehydration solution is the most efficient method to treat cholera; however, it does not interfere in the action mechanism of the main virulence factor produced by Vibrio cholerae, the cholera toxin (CT), and this disease still stands out as a problem for human health worldwide. This review aimed to describe therapeutic alternatives available in the literature, especially those related to the search for molecules acting upon the physiopathology of cholera.

Key Findings: New molecules have offered a protection effect against diarrhoea induced by CT or even by infection from V. cholerae. The receptor regulator cystic fibrosis channel transmembrane (CFTR), monosialoganglioside (GM1), enkephalinase, AMP-activated protein kinase (AMPK), inhibitors of expression of virulence factors and activators of ADP-ribosylarginine hydrolase are the main therapeutic targets studied. Many of these molecules or extracts still present unclear action mechanisms.

Conclusions: Knowing therapeutic alternatives and their molecular mechanisms for the treatment of cholera could guide us to develop a new drug that could be used in combination with the rehydration solution.
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http://dx.doi.org/10.1111/jphp.13344DOI Listing
December 2020

Ultra-diluted impairs ovine oocyte viability and maturation after culture.

Anim Reprod 2020 Jun 18;17(2):e20190100. Epub 2020 Jun 18.

Ciência do Centro de Saúde, Universidade Estadual do Ceará, Fortaleza, CE, Brasil.

This study investigated the effect of on the oocyte meiosis resumption and viability rates, progesterone production and mitochondrial activity after maturation of cumulus-oocyte complexes (COCs) in sheep. Sheep ovaries were collected at a local slaughterhouse and COCs were recovered by slicing technique. The selected COCs were maturated in TCM199 (Control treatment), or control medium supplemented with 0.05% ethanol (v/v) (the vehicle of the homeopathic preparation - Ethanol treatment) or with . After 24 h of maturation (IVM), oocytes were mechanically denuded and incubated with Hoechst 33342 and MitoTracker (0.5 μM) Orange CMTMRos for analysis of viability and chromatin configuration, and mitochondrial activity, respectively. The results showed that addition increased oocyte degeneration and reduced meiotic resumption compared to the control (P < 0.05). Interestingly, the percentages meiotic resumption and oocyte maturation were lower in the treatment compared to its vehicle (Ethanol treatment) (P < 0.05). On the other hand, when the treatments were compared, higher mitochondrial activity was observed in the Ethanol treatment (P < 0.05). In conclusion, contrary to its vehicle, the addition of to the IVM medium promoted oocyte degeneration and affected negatively the mitochondrial distribution, impairing meiosis resumption.
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http://dx.doi.org/10.1590/1984-3143-AR2019-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375870PMC
June 2020

Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

J Periodontal Res 2020 Dec 25;55(6):877-886. Epub 2020 Jun 25.

Medicinal Plants Research Center (NPPM), Federal University of hPiaui, Teresina, Brazil.

Background And Objective: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (βCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis.

Material And Methods: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-βCD (ligature), and 25 mg/kg of αTPN-βCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy.

Results: The treatment with αTPN-βCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-βCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis.

Conclusion: The results obtained suggest that the treatment with αTPN-βCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-βCD.
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http://dx.doi.org/10.1111/jre.12780DOI Listing
December 2020

Anethole Supplementation During Oocyte Maturation Improves In Vitro Production of Bovine Embryos.

Reprod Sci 2020 08;27(8):1602-1608

Laboratory of Manipulation of Oocytes and Preantral Follicles (LAMOFOPA), Faculty of Veterinary Medicine, State University of Ceara, Av Dr Silas Munguba, 1700, Campus do Itaperi, Fortaleza, Ceara, Brazil.

Oxidative stress is one of the most detrimental factors that affect oocyte developmental competence and embryo development in vitro. The impact of anethole supplementation to in vitro maturation (IVM) media on oocyte maturation and further bovine in vitro embryo production was investigated. Oocytes of slaughterhouse-derived bovine ovaries were placed in IVM with anethole at different concentrations of 30 (AN30), 300 (AN300), and 2000 μg/mL (AN2000), or without (control treatment). The oocytes were assessed for maturation rates, and for reactive oxygen species (ROS) and ferric reducing antioxidant power (FRAP) levels, and mitochondrial membrane potential. Embryo development was assessed by cleavage and blastocyst rates, and embryo cell number. The percentage of metaphase II oocytes were similar among the treatments (range, 77%-96%). Anethole at 300 μg/mL was the only treatment that yielded higher cleavage and embryo development (morula and blastocyst) rates compared to the control treatment. The ROS production in the oocytes after maturation did not differ among treatments. However, oocytes treated with anethole at 300 μg/mL had higher (P < .05) FRAP and mitochondrial membrane potential compared to the control treatment. Furthermore, AN300 treatment increased (P < .05) the average number of total cells in blastocysts compared to the control and AN30 treatments. The use of anethole at 300 μg/mL during IVM is suggested to improve the quantity and quality of bovine embryos produced in vitro. The beneficial effects of anethole on embryonic developmental competence in vitro seems to be related to its capacity to regulate the redox balance and improve mitochondrial function in oocytes and embryos.
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http://dx.doi.org/10.1007/s43032-020-00190-xDOI Listing
August 2020

Yeast in plant phytotelmata: Is there a "core" community in different localities of rupestrian savannas of Brazil?

Braz J Microbiol 2020 Sep 8;51(3):1209-1218. Epub 2020 May 8.

Departamento de Microbiologia, ICB, C.P. 486, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.

Ephemeral microbial communities usually undergo priority effect and result in higher diversity with a few representatives of each species. Community structure of yeasts in bromeliad tanks was compared between two rupestrian savanna (Cerrado) areas in Brazil and to yeasts isolated from water holes in the same areas. Water samples were collected from 60 tanks of bromeliads Bromelia karatas and Encholirium sp. and rock holes at the Karstic Area of Aurora, Tocantins State and 60 tanks of Vriesea minarum (Bromeliaceae) and Paepalanthus bromelioides (Eriocaulaceae) at Serra do Cipó National Park, Minas Gerais State in Brazil. The yeast diversity comprised 90 species from which 60% are basidiomycetous yeasts usually associated with phylloplane, soils, and aquatic habitats. The species Papiliotrema laurentii, Rhodotorula mucilaginosa, Pa. nemorosus, and Pseudozyma hubeiensis were the most frequent species associated with bromeliads. Eighteen yeast species, two ascomycetous and 16 basidiomycetous, were consistently isolated from the substrates in both areas and may represent a core community in bromeliads in rupestrian fields. Singlets occurred in 38 to 69% of samples, and 32 species were isolated only once. Our findings reinforce the ephemeral nature of the yeast communities associated with tank-forming plants in which individual phytotelmata act as patches or aquatic islands prone to rapid colonization-extinction rates receiving inocula from plant and soil debris. Ephemeral rock holes also represent a transitory habitat for yeast species associated with plants and soil.
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http://dx.doi.org/10.1007/s42770-020-00286-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455655PMC
September 2020

The neuroprotective effect of Riparin IV on oxidative stress and neuroinflammation related to chronic stress-induced cognitive impairment.

Horm Behav 2020 06 28;122:104758. Epub 2020 Apr 28.

Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

Background: Cognitive impairment is identified as one of the diagnostic criteria for major depressive disorder and can extensively affect the quality of life of patients. Based on these findings, this study aimed to investigate the possible effects of Riparin IV (Rip IV) on cognitive impairment induced by chronic administration of corticosterone in mice.

Methods: Female Swiss mice were divided into four groups: control (Control), corticosterone (Cort), Riparin IV (Cort + Rip IV), and Fluvoxamine (Cort + Flu). Three groups were administered corticosterone (20 mg/kg) subcutaneously during the 22-day study, while the control group received only vehicle. After the 14th day, the groups were administered medications: Riparin IV (Rip IV), fluvoxamine (Flu), or distilled water, by gavage, 1 h after the subcutaneous injections. After treatment, mice underwent behavioral testing, and brain areas were removed for oxidative stress and cytokine content assays.

Results: The results revealed that Cort-treated mice developed a cognitive impairment and exhibited a neuroinflammatory profile with an oxidative load and Th1/Th2 cytokine imbalance. Rip IV treatment significantly ameliorated the cognitive deficit induced by Cort and displayed a neuroprotective effect.

Conclusion: The antidepressant-like ability of Rip IV treatment against chronic Cort-induced stress may be due to its potential to mitigate inflammatory damage and oxidative stress. The antioxidant and anti-inflammatory effect observed indicates Rip IV as a possible drug for antidepressant treatment of non-responsive patients with severe and cognitive symptoms.
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http://dx.doi.org/10.1016/j.yhbeh.2020.104758DOI Listing
June 2020

Antidiarrheal activity of farnesol in rodents: Pharmacological actions and molecular docking.

Eur J Pharmacol 2020 May 4;874:172986. Epub 2020 Feb 4.

Post-Graduation Program in Biotechnology (RENORBIO), Federal University of Piauí, Teresina, PI, Brazil; Medicinal Plants Research Center (NPPM), Federal University of Piauí, Teresina, PI, Brazil. Electronic address:

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (CHO), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.
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http://dx.doi.org/10.1016/j.ejphar.2020.172986DOI Listing
May 2020

Biopolymer Extracted from (Red Angico Gum) Exerts Therapeutic Potential in Mice: Antidiarrheal Activity and Safety Assessment.

Pharmaceuticals (Basel) 2020 Jan 18;13(1). Epub 2020 Jan 18.

The Northeast Biotechnology Network (RENORBIO), Federal University of Piauí, Teresina, PI 64049-550, Brazil.

var. cebil (Griseb.) Altschul (Fabaceae family), commonly known as the red angico tree, is a medicinal plant found throughout Brazil's semi-arid area. In this study, a chemical analysis was performed to investigate the antidiarrheal activity and safety profile of red angico gum (RAG), a biopolymer extracted from the trunk exudate of . Upon FT-IR spectroscopy, RAG showed bands in the regions of 1608 cm, 1368 cm, and 1029 cm, which relate to the vibration of O-H water molecules, deformation vibration of C-O bands, and vibration of the polysaccharide C-O band, respectively, all of which are relevant to glycosidic bonds. The peak molar mass of RAG was 1.89 × 10 g/mol, with the zeta potential indicating electronegativity. RAG demonstrated high yield and solubility with a low degree of impurity. Pre-treatment with RAG reduced the total diarrheal stool and enteropooling. RAG also enhanced Na+/K+-ATPase activity and reduced gastrointestinal transit, and thereby inhibited intestinal smooth muscle contractions. Enzyme-Linked Immunosorbent Assay (ELISA) demonstrated that RAG can interact with GM1 receptors and can also reduce -induced diarrhea in vivo. Moreover, RAG did not induce any signs of toxicity in mice. These results suggest that RAG is a possible candidate for the treatment of diarrheal diseases.
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http://dx.doi.org/10.3390/ph13010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168896PMC
January 2020

Activation of goat primordial follicles in vitro: Influence of alginate and ovarian tissue.

Reprod Domest Anim 2020 Jan 27;55(1):105-109. Epub 2019 Nov 27.

Laboratory of Manipulation of Oocytes and Preantral Follicles (LAMOFOPA), State University of Ceará, Fortaleza, Brazil.

The present study aimed to evaluate the effect of three culture systems on caprine primordial follicle activation in vitro: follicles cultured either in the isolated form within alginate (Isolated follicles + Alginate treatment), or enclosed in ovarian tissue (in situ), with or without alginate (Fragment + Alginate, and Fragment alone treatments, respectively). After culture, the Isolated follicles + Alginate treatment presented a percentage of morphologically normal follicles (MNF) similar to both the non-cultured control and the Fragment Alone treatments. Nevertheless, Fragment + Alginate treatment showed a significant reduction in the number of MNF when compared to the other treatments. Regarding follicle development, our results showed that regardless of the alginate, the presence of ovarian tissue limited primordial follicle activation during in vitro culture. Remarkably, the Isolated primordial follicle + Alginate treatment was the only one that significantly promoted follicle activation and increased both follicle and oocyte diameters during IVFC, pointing out a higher cell proliferation. In conclusion, the presence of ovarian tissue with or without alginate limited follicle development (activation) after culture. Nevertheless, when primordial follicles were isolated and encapsulated in alginate they presented suitable survival rates, higher rates of follicle activation and continued to grow throughout the culture period.
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http://dx.doi.org/10.1111/rda.13582DOI Listing
January 2020

Thymol reverses depression-like behaviour and upregulates hippocampal BDNF levels in chronic corticosterone-induced depression model in female mice.

J Pharm Pharmacol 2019 Dec 14;71(12):1774-1783. Epub 2019 Oct 14.

Drug Research and Development Center-NPDM, Federal University of Ceará, Fortaleza, Brazil.

Objectives: Based on this, the central therapeutic effects of thymol were verified in the neurotrophic pathway.

Methods: Female swiss mice were divided into four groups: control, corticosterone (Cort), thymol (Cort + thymol) and fluvoxamine (Cort + Flu). The administration of corticosterone was used to induce depressive symptoms for 23 days. After the treatment, the animals were exposed the behavioural tests, such as forced swimming test, tail suspension test, sucrose preference test, light/dark test, social interaction test, Y-maze test, plus-maze test and hole-board test. The hippocampus was also removed, and BDNF was measured by ELISA and Western blot.

Key Findings: As a result, thymol and fluvoxamine were able to reverse the depressive symptoms, as well as to improve the anxious frame. The anhedonic and short-term memory was restored with the treatment. In the neurochemical tests, both thymol and fluvoxamine restored BDNF levels, improving the depressive condition.

Conclusions: This work opens up new investigations aiming at the use of this molecule as a therapeutic alternative for treating depression disorders.
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http://dx.doi.org/10.1111/jphp.13162DOI Listing
December 2019

High Exploratory Phenotype Rats Exposed to Environmental Stressors Present Memory Deficits Accompanied by Immune-Inflammatory/Oxidative Alterations: Relevance to the Relationship Between Temperament and Mood Disorders.

Front Psychiatry 2019 5;10:547. Epub 2019 Aug 5.

Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceara, Fortaleza, Brazil.

Low-exploratory (LE) and high-exploratory (HE) rodents mimic human depressive and hyperthymic temperaments, respectively. Mood disorders (MD) may be developed by the exposure of these temperaments to environmental stress (ES). Psychiatric symptoms severity in MD patients is related to the magnitude of memory impairment. Thus, we aimed at studying the consequences of the exposure of LE and HE male Wistar rats, during periadolescence, to a combination of ES, namely, paradoxical sleep deprivation (PSD) and unpredictable stress (US), on anxiety-related behavior in the plus maze test, working (WM) and declarative memory (DM) performance. We also evaluated hippocampal immune-inflammatory/oxidative, as consequences of ES, and prevention of ES-induced alterations by the mood-stabilizing drugs, lithium and valproate. Medium exploratory (ME) control rats were used for comparisons with HE- and LE-control rats. We observed that HE-controls presented increased anxiolytic behavior that was significantly increased by ES exposure, whereas LE-controls presented increased anxiety-like behavior relative to ME-controls. Lithium and valproate prevented anxiolytic alterations in HE+ES rats. HE+ES- and LE+ES-rats presented WM and DM deficits. Valproate and lithium prevented WM deficits in LE-PSD+US rats. Lithium prevented DM impairment in HE+ES-rats. Hippocampal levels of reduced glutathione (GSH) increased four-fold in HE+ES-rats, being prevented by valproate and lithium. All groups of LE+ES-rats presented increased levels of GSH in relation to controls. Increments in lipid peroxidation in LE+ES- and HE+ES-rats were prevented by valproate in HE+ES-rats and by both drugs in LE+ES-rats. Nitrite levels were increased in HE+ES- and LE+ES-rats (five-fold increase), which was prevented by both drugs in LE+ES-rats. HE+ES-rats presented a two-fold increase in the inducible nitric oxide synthase (iNOS) expression that was prevented by lithium. HE+ES-rats showed increased hippocampal and plasma levels of interleukin (IL)-1β and IL-4. Indoleamine 2, 3-dioxygenase 1 (IDO1) was increased in HE+ES- and LE+ES-rats, while tryptophan 2,3-dioxygenase (TDO2) was increased only in HE+ES-rats. Altogether, our results showed that LE- and HE-rats exposed to ES present distinct anxiety-related behavior and similar memory deficits. Furthermore, HE+ES-rats presented more brain and plasma inflammatory alterations that were partially prevented by the mood-stabilizing drugs. These alterations in HE+ES-rats may possibly be related to the development of mood symptoms.
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http://dx.doi.org/10.3389/fpsyt.2019.00547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689823PMC
August 2019

Proteins from Plumeria pudica latex exhibit protective effect in acetic acid induced colitis in mice by inhibition of pro-inflammatory mechanisms and oxidative stress.

Life Sci 2019 Aug 5;231:116535. Epub 2019 Jun 5.

Universidade Federal do Piauí, Campus Ministro Reis Velloso, Laboratório de Bioquímica de Plantas Laticíferas (LBPL), CEP 64.202-020 Parnaíba, Piauí, Brazil. Electronic address:

Latex proteins from P. pudica (LPPp) have anti-inflammatory activity. In the present study, LPPp was evaluated to protect animals against inflammatory ulcerative colitis (UC). UC was induced by intracolonic instillation of a 6% acetic acid solution and the animals received LPPp (10, 20 or 40 mg/kg) by intraperitoneal route 1 h before and 17 h after acetic acid injection. Eighteen hours after instillation of acetic acid, the mice were euthanized and the colons were excised to determine the wet weight, macroscopic and microscopic lesion scores, myeloperoxidase (MPO) activity, IL1-β levels, glutathione (GSH) and malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. The results revealed that LPPp treatment (40 mg/kg) had a protective effect on acetic acid-induced colitis by reducing the wet weight, macroscopic and microscopic scores of intestinal lesions and colonic MPO activity. Additionally, LPPp inhibited tissue oxidative stress, since decreases in GSH consumption, MDA concentration and SOD activity were observed. The treatment with LPPp reduced the levels of cytokine IL-1β, contributing to the reduction of colon inflammation. Biochemical investigation showed that LPPp comprises a mixture of proteins containing proteinases, chitinases and proteinase inhibitors. These data suggest that LPPp has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine release and oxidative stress.
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http://dx.doi.org/10.1016/j.lfs.2019.06.010DOI Listing
August 2019

Early ovine preantral follicles have a potential to grow until antral stage in two-step culture system in the presence of aqueous extract of Justicia insularis.

Reprod Domest Anim 2019 Aug 17;54(8):1121-1130. Epub 2019 Jun 17.

Laboratory of Manipulation of Oocyte and Ovarian Preantral Follicles (LAMOFOPA), Faculty of Veterinary (FAVET), State University of Ceará, Fortaleza, Brazil.

The objective of this study was to determine whether preantral follicles cultured in vitro for 7 days within ovine ovarian cortical strips could be isolated at the secondary follicles (SF) and grown until antral stage during an additional 6 days period of in vitro culture in the presence of aqueous extract of Justicia insularis. Fresh ovarian fragments from 16 adult sheep were fixed for histological analysis (Control 1) or in vitro cultured individually in α-MEM supplemented with 0.3 mg/ml J. insularis (Step 1) for 7 days. Part of the fragments then were fixed for histological analysis (in vitro culture group). Remaining fragments were exposed stepwise to increasing trehalose concentrations before immediate isolation of SF and viability assessment (Control 2) or after 6 days of culture in α-MEM supplemented with 0.3 mg/ml J. insularis (Step 2). In Step 1, percentage of follicular activation was 80%. In Step 2, a significant increase (p < 0.05) in follicular diameter and antrum formation within 6 days in vitro culture of isolated follicles was achieved. The total antioxidant capacity from both steps significantly increase (p < 0.05) from day 2 to day 6. Confocal analysis of oocytes showed 57.14% oocytes with homogeneous distribution and 42.86% with peri-cortical distribution. In conclusion, SF can be successfully isolated from sheep ovarian cortex after 7 days of culture and are capable of surviving and forming an antral cavity if cultured in vitro for an additional 6 days in the presence of 0.3 mg/ml J. insularis.
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http://dx.doi.org/10.1111/rda.13477DOI Listing
August 2019

Alendronate-induced gastric damage in normoglycemic and hyperglycemic rats is reversed by metformin.

Eur J Pharmacol 2019 Aug 25;856:172410. Epub 2019 May 25.

Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (Lafidg), Federal University of Piauí, Av. São Sebastião, 2819, Parnaíba, PI, CEP 64202-020, Brazil. Electronic address:

Alendronate is a bisphosphonate widely used for the treatment of osteoporosis; however, one of its main adverse reactions is gastric ulcer. Metformin is an oral antihyperglycemic agent that has several beneficial effects, including healing, gastroprotective and anti-tumoral action. This study aimed to evaluate the gastroprotective activity of metformin in alendronate-induced gastric damage in normoglycemic and hyperglycemic rats. The treatment with 100 mg/kg of metformin showed a significant gastroprotective effect in damage induced by alendronate (50 mg/kg) in macroscopic analysis and the analysis of light microscopy and atomic force microscopy. The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6), myeloperoxidase activity, and malondialdehyde levels. Also, the results suggested that metformin induces the maintenance of basal levels of collagen and increase the production of mucus. Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action. The gastroprotective effect of metformin might be related to the activation of the AMPK pathway. These findings revealed that metformin has a gastroprotective action and may be considered a therapeutic potential for the prevention and treatment of gastric lesions induced by alendronate.
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http://dx.doi.org/10.1016/j.ejphar.2019.172410DOI Listing
August 2019

Antiulcer and Antioxidant Activity of a Lectin from Mucuna pruriens Seeds on Ethanol- induced Gastropathy: Involvement of Alpha-2 Adrenoceptors and Prostaglandins.

Curr Pharm Des 2019 ;25(12):1430-1439

Federal University of Ceara, Master of Biotechnology Degree Program, Sobral - Ceara, Brazil.

Ethnopharmacological Relevance: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice.

Material And Methods: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action.

Results: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects.

Conclusion: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.
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http://dx.doi.org/10.2174/1381612825666190524081433DOI Listing
February 2020

Reversal effect of Riparin IV in depression and anxiety caused by corticosterone chronic administration in mice.

Pharmacol Biochem Behav 2019 05 20;180:44-51. Epub 2019 Mar 20.

Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address:

Mental disorders have a multifactorial etiology and stress presents as one of the causal factors. In depression, it is suggested that high cortisol concentration contributes directly to the pathology of this disease. Based on that, the study aims to evaluate the potential antidepressant effect of Riparin IV (Rip IV) in mice submitted to chronic stress model by repeated corticosterone administration. Female Swiss mice were selected into four groups: control (Ctrl), corticosterone (Cort), Riparin IV (Cort + Rip IV) and fluvoxamine (Cort + Flu). Three groups were administrated subcutaneously (SC) with corticosterone (20 mg/kg) during twenty-one days, while the control group received only vehicle. After the fourteenth day, groups were administrated tested drugs: Riparin IV, fluvoxamine or distilled water, by gavage, 1 h after subcutaneous injections. After the final treatment, animals were exposed to behavioral models such as forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM) and sucrose preference test (SPT). The hippocampus was also removed for the determination of BDNF levels. Corticosterone treatment altered all parameters in behavioral tests, leading to a depressive- and anxious-like behavior. Riparin IV and fluvoxamine exhibit antidepressant effect in FST, TST and SPT. In EPM and OFT, treatment displayed anxiolytic effect without alteration of locomotor activity. Corticosterone administration decreased BDNF levels and Riparin IV could reestablish them, indicating that its antidepressant effect may be related to ability to ameliorate hippocampal neurogenesis. These findings suggest that Riparin IV improves the depressive and anxious symptoms after chronic stress and could be a new alternative treatment for patients with depression.
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http://dx.doi.org/10.1016/j.pbb.2019.03.005DOI Listing
May 2019

Anethole Supplementation During Oocyte Maturation Improves In Vitro Production of Bovine Embryos.

Reprod Sci 2019 Feb 26:1933719119831783. Epub 2019 Feb 26.

1 Laboratory of Manipulation of Oocytes and Preantral Follicles (LAMOFOPA), Faculty of Veterinary Medicine, State University of Ceara, Fortaleza, Ceara, Brazil.

Oxidative stress is one of the most detrimental factors that affect oocyte developmental competence and embryo development in vitro. The impact of anethole supplementation to in vitro maturation (IVM) media on oocyte maturation and further bovine in vitro embryo production was investigated. Oocytes of slaughterhouse-derived bovine ovaries were placed in IVM with anethole at different concentrations of 30 (AN30), 300 (AN300), and 2000 μg/mL (AN2000), or without (control treatment). The oocytes were assessed for maturation rates, and for reactive oxygen species (ROS) and ferric reducing antioxidant power (FRAP) levels, and mitochondrial membrane potential. Embryo development was assessed by cleavage and blastocyst rates, and embryo cell number. The percentage of metaphase II oocytes were similar among the treatments (range, 77%-96%). Anethole at 300 µg/mL was the only treatment that yielded higher cleavage and embryo development (morula and blastocyst) rates compared to the control treatment. The ROS production in the oocytes after maturation did not differ among treatments. However, oocytes treated with anethole at 300 µg/mL had higher ( P < .05) FRAP and mitochondrial membrane potential compared to the control treatment. Furthermore, AN300 treatment increased ( P < .05) the average number of total cells in blastocysts compared to the control and AN30 treatments. The use of anethole at 300 μg/mL during IVM is suggested to improve the quantity and quality of bovine embryos produced in vitro. The beneficial effects of anethole on embryonic developmental competence in vitro seems to be related to its capacity to regulate the redox balance and improve mitochondrial function in oocytes and embryos.
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http://dx.doi.org/10.1177/1933719119831783DOI Listing
February 2019

High-fat diet aggravates the liver disease caused by periodontitis in rats.

J Periodontol 2019 09 27;90(9):1023-1031. Epub 2019 May 27.

Laboratory of Histological Analysis and Preparation (LAPHis), Federal University of Piauí, Parnaíba, Piauí, Brazil.

Background: Periodontitis is an inflammatory disease that causes periodontium and hepatic alterations. Liver disease is related to the intake of foods rich in fat and sugars (high-fat). The objective of this study was to evaluate whether a high-fat diet can aggravate the liver disease caused by ligature-induced periodontitis in rats.

Methods: Twenty-one female rats were divided into three groups (n = 7 in each group): control; periodontitis (periodontitis induced with ligature) and high-fat + periodontitis (received hypercaloric diet and induction of periodontitis). The rats were submitted to the analyses of the following periodontal parameters: gingival bleeding index (GBI), probing pocket depth (PPD), tooth mobility (TM), and alveolar bone height. In the hepatic tissue, the levels of malondialdehyde (MDA), glutathione (GSH), total cholesterol, and myeloperoxidase activity (MPO) were measured. Liver samples were also histopathologically evaluated. Finally, blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, cholesterol high-density lipoprotein (HDL), and uric acid were measured.

Results: The high-fat + periodontitis group presented an increase in the steatosis score (P < 0.05) for the histopathologic evaluation, when compared with the periodontitis group. MDA, uric acid and ALT levels also increased, whereas GSH and HDL levels showed lower values.

Conclusion: A high-fat diet aggravates the liver disease caused by ligature-induced periodontitis in rats.
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http://dx.doi.org/10.1002/JPER.18-0564DOI Listing
September 2019

Lactobacillus reuteri DSM 17938 Protects against Gastric Damage Induced by Ethanol Administration in Mice: Role of TRPV1/Substance P Axis.

Nutrients 2019 Jan 21;11(1). Epub 2019 Jan 21.

Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (Lafidg), Federal University of Piauí, Av. São Sebastião, nº 2819, CEP 64202-02, Parnaíba, PI, Brazil.

This study aimed to evaluate the effect of DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 10⁸ CFU•g body wt•day of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 μmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.
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http://dx.doi.org/10.3390/nu11010208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356937PMC
January 2019

Inhibition of neutrophil migration and reduction of oxidative stress by ethyl p-coumarate in acute and chronic inflammatory models.

Phytomedicine 2019 Apr 27;57:9-17. Epub 2018 Sep 27.

Medicinal Plants Research Center, Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550 Teresina, Piauí, Brazil. Electronic address:

Background: It is well known that medicinal plants and their products are relevant candidates for the treatment of inflammatory conditions. Ethyl p-coumarate is a phenylpropanoid that has similar structure to others anti-inflammatory and antioxidant substances. However, these activities have never been tested.

Purpose: The aim of this study was to investigate the effect of ethyl p-coumarate on inflammatory and oxidative stress parameters.

Study Design: This is an experimental study to evaluate the anti-inflammatory and antioxidant activities of ethyl p-coumarate in acute and chronic models of inflammation.

Methods: The anti-inflammatory effect of ethyl p-coumarate was evaluated in Swiss mice by carrageenan-induced paw edema model (1%, 50 μl), followed by histological analysis, and edema induced by compound 48/80 (12 µg/paw), histamine (100  µg/paw), serotonin (100 µg/paw) and prostaglandin E2 (3 nmol/paw) in comparison to indomethacin treatment (10 mg/kg, p.o.). In addition, peritonitis was induced by carrageenan (500 μg/cavity) to neutrophil and total leukocytes counting, myeloperoxidase (MPO), interleukin 6 (IL-6) and 8 (IL-8), nitrite (NO), glutathione (GSH) and malondialdehyde (MDA) measurements. The arthritis model was induced with Freund's complete adjuvant (id. 0.1 ml) in female Wistar rats, with measurement of joint diameter and X-ray. Changes in gastric tissue of Swiss mice were analyzed in comparison to indomethacin (20  mg/kg, p.o.).

Results: After treatment with ethyl p-coumarate, the animals had no apparent toxic effects, and significantly inhibited paw edema induced by edematogenic agents, neutrophil (p < 0.001) and total leukocyte (p < 0.001) migration, MPO (p < 0.01), IL-6 (p < 0.05) and IL-8 (p < 0.5), MDA (p < 0.5), GSH (p < 0.5), NO (p < 0.001), joint thickness and bones changes. Furthermore, were not observed significant formation of gastric lesions.

Conclusion: Taken together, these results suggest that ethyl p-coumarate exhibits anti-inflammatory activity through the inhibition of inflammatory mediators and leukocyte migration without causing gastric lesions.
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http://dx.doi.org/10.1016/j.phymed.2018.09.034DOI Listing
April 2019
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