Publications by authors named "Ayman M Mahmoud"

94 Publications

Galangin attenuates diabetic cardiomyopathy through modulating oxidative stress, inflammation and apoptosis in rats.

Biomed Pharmacother 2021 Mar 19:111410. Epub 2021 Mar 19.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt; Biotechnology Department, Research Institute of Medicinal and Aromatic Plants, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address:

Cardiovascular complications are the leading cause of morbidity in diabetes. Oxidative stress and inflammation are implicated in the development and progression of diabetic cardiomyopathy (DCM). This study explored the cardioprotective effect of galangin (Gal), a natural flavonoid with radical-scavenging and anti-inflammatory activities, in diabetic rats. An experimental diabetic rat model was achieved by a single injection of 50 mg/kg streptozotocin. Gal (15 mg/kg) was administered daily for six weeks and the samples were then collected. Diabetic rats exhibited hyperglycemia, increased glycosylated hemoglobin, triglycerides and cholesterol levels and reduced serum insulin. Serum troponin I, CK-MB and LDH were increased in diabetic rats. Furthermore, hearts of diabetic rats were characterized by elevated malondialdehyde, protein carbonyl, NF-κB p65, TNF-α, IL-1β, iNOS, IL-6, Bax, caspase-3 and 8-Oxo-dG, and decreased superoxide dismutase, catalase, reduced GSH, and Bcl-2. Gal ameliorated hyperglycemia, dyslipidemia, and heart function markers, and prevented histopathological alterations in diabetic rats. In addition, Gal attenuated cardiac oxidative injury, inflammation and apoptosis, and boosted antioxidant defenses. In conclusion, Gal has a protective effect on cardiomyopathy by attenuating hyperglycemia, dyslipidemia, oxidative stress and inflammation in diabetic rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111410DOI Listing
March 2021

Linagliptin mitigates experimental inflammatory bowel disease in rats by targeting inflammatory and redox signaling.

Life Sci 2021 May 2;273:119295. Epub 2021 Mar 2.

Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

Aims: Dipeptidyl peptidase-4 (DPP-4) has been involved in the pathogenesis of inflammatory bowel diseases (IBD), yet the underlying mechanisms remain inconclusive. The present study aimed to investigate the potential of linagliptin, a potent/selective DPP-4 inhibitor with marked anti-inflammatory actions, to attenuate trinitrobenzene sulfonic acid (TNBS)-evoked colitis in rats; an experimental model of IBD, and the implicated molecular mechanisms. This may add to the clinical utility of linagliptin for the management of patients with coexisting IBD and diabetes mellitus. Notably, no former studies have linked JAK2/STAT3, HMGB1/NF-κB, and Nrf2/HO-1 signaling in TNBS-evoked colitis.

Materials And Methods: Western blotting and ELISA were used to determine the levels of target signals.

Key Findings: Administration of linagliptin (1.5 mg/kg; p.o.) mitigated the colitis severity via diminishing the disease activity index, colon weight/length ratio, and macroscopic scores. Linagliptin also lowered the colonic histologic scores and leukocyte invasion. Notably, linagliptin inhibited the colonic DPP-4 activity and upregulated the expression of intestinotrophic GLP-2 without incurring hypoglycemia in animals. Linagliptin curbed inflammation through the suppression of colonic IL-6, TNF-α, and myeloperoxidase and upregulation of IL-10. It also inhibited the IL-6/JAK2/STAT3 pathway via downregulating p-JAK2/JAK2 and p-STAT3/STAT3 protein expression and HMGB1/RAGE/NF-κB cascade through lowering HMGB1, RAGE, and p-NF-κB p65/NF-κB p65 protein expression. In the context of mucosal oxidative stress, linagliptin diminished lipid peroxides and augmented GSH, GPx, and total antioxidant capacity. It also activated Nrf2/HO-1 pathway via upregulating Nrf2 and HO-1 protein expression.

Significance: Linagliptin shows a promise for the management of IBD via targeting IL-6/JAK2/STAT3, HMGB1/RAGE/NF-κB, and Nrf2/HO-1 pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119295DOI Listing
May 2021

Risk of drug resistance and repeated infection with Klebsiella pneumoniae and Escherichia coli in intensive care unit cancer patients.

Comb Chem High Throughput Screen 2021 Jan 20. Epub 2021 Jan 20.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University. Egypt.

Background: Bacterial infection is a frequent complication in cancer and immunocompromised patients. The emergence of antibiotic resistance is a significant health problem and cancer patients are at risk of repeated infections with drug-resistant bacteria.

Objective: This investigation aimed to identify predictors of repeat infections of Escherichia coli and Klebsiella pneumoniae and drug resistance in cancer patients admitted to the intensive care unit (ICU) in Upper Egypt.

Methods: Blood, urine, sputum, pus, and mouth and nose swabs were collected form patients at the Pediatric Oncology and Medical Oncology ICUs during the period from February 2017 to May 2018. The samples were assessed by antibiotic susceptibility test and further evaluated by genetic testing for the temoniera (TEM) gene of β-lactamase. Samples positive for K. pneumoniae and E. coli were included and isolates positive for other microorganisms were excluded.

Results: The study included 107 patients with malignant neoplasms and 136 samples. Repeated infection with K. pneumoniae and E. coli occurred in 31% and 22.45% of patients, respectively. Patients stayed for a longer period in the ICU were more likely to have repeated infections (OR 1.25, 95%CI 1.10-1.44, p=0.001) after control of other confounding factors. The type of malignant neoplasm whether it was hematologic or solid tumor (OR 7.46, 95% CI 2.56-21.7, p=0.0002) and a longer prior stay in the ICU (OR 1.14, 95% CI 1.02-1.28, p=0.025) remained the independent predictors for the drug resistance in the last infection. The TEM type of β-lactamase was encoded in 48.68% and 66.67% of K. pneumoniae and E. coli, respectively.

Conclusion: Reinfection with K. pneumoniae and E. coli in patients with cancer can occur as the number of days in the hospital increases. Total prior days spent in the ICU by cancer patients were independently associated with both repeated infections and drug resistance. Samples from patients with hematologic neoplasms were associated with drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1386207324666210121104724DOI Listing
January 2021

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors at the National Blood Bank, Amman, Jordan.

Medicina (Kaunas) 2020 Dec 16;56(12). Epub 2020 Dec 16.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Blood screening is considered a compulsory procedure in health care services to reduce the occurrence of transfusion transmitted infections (TTIs). This study estimated the distribution rates of ABO and Rh blood group systems, prevalence rates of TTIs among blood donors and their association with the ABO blood group and Rh system. A retrospective study was conducted at the national blood bank, Amman, Jordan for a period of 6 years (from January 2013 to December 2018). For TTIs analysis, about 5 mL blood sample was collected from each volunteer. A total of 365,029 persons (346,048 (94.8%) males and 18,981 (5.2%) females) donated their blood at the national blood bank, Amman, Jordan from January 2013 to December 2018. The results revealed that O and A were the most prevalent blood groups (37.44% and 36.82%, respectively), followed by B (18.62%) and AB (7.12%). The distribution of Rh + ve and Rh - ve among blood donors showed that Rh + ve donors were more prevalent (88.73%) compared with Rh - ve (11.27%). HBsAg was the most prevalent viral infection (0.38%) followed by HCV (0.13%), syphilis (0.02%), HIV (0.006%) and the male donors were highly infected when compared with female donors. The association between ABO/Rh blood groups and TTIs infections was nonsignificant. In conclusion, low frequency rates of TTIs among blood donors were detected in the current study, but improvements are still continuously required. Low percentages of female donors need to be managed via conducting health cultural education programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina56120701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765551PMC
December 2020

Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats.

Drug Des Devel Ther 2020 30;14:5275-5288. Epub 2020 Nov 30.

Zoology Department Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Introduction: Cyclophosphamide (CP) causes redox imbalance and its use is associated with marked cardiotoxicity that limits its clinical applications. The present study investigated the protective effects of acetovanillone (AV) and edaravone (ED) against CP-induced oxidative stress and cardiac damage, emphasizing the role of PI3K/Akt/mTOR and Nrf2 signaling.

Materials And Methods: Rats received either AV (100 mg/kg) or ED (20 mg/kg) orally for 10 days and CP (200 mg/kg) on day 7. At day 11, the rats were sacrificed, and samples were collected for analysis.

Results: AV and ED ameliorated serum troponin I, CK-MB, LDH, AST and ALP, and prevented cardiac histological alterations in CP-intoxicated rats. Both treatments decreased cardiac lipid peroxidation and enhanced GSH, SOD and cytoglobin in CP-induced rats. AV and ED downregulated Keap1, whereas increased the expression of PI3K, Akt, mTOR and Nrf2 in the heart of rats received CP. Additionally, the binding modes of AV and ED to Keap1 were pinpointed in silico using molecular docking simulations.

Conclusion: AV and ED prevent CP cardiotoxicity by attenuating oxidative stress and tissue injury, and modulating cytoglobin, and PI3K/Akt/mTOR and Keap1/Nrf2 signaling. Therefore, AV and ED may represent promising agents that can prevent cardiac injury in patients receiving CP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S281854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721127PMC
November 2020

Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling.

Drug Des Devel Ther 2020 29;14:4003-4019. Epub 2020 Sep 29.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Introduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation.

Materials And Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks.

Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pb-induced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats.

Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S265636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532898PMC
September 2020

Acute inflammation and oxidative stress induced by lipopolysaccharide and the ameliorative effect of stingless bee honey.

Comb Chem High Throughput Screen 2020 Sep 18. Epub 2020 Sep 18.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor. Malaysia.

Background: Systemic acute inflammation is the hallmark of sepsis and associated with multiple organ dysfunction.

Objective: This study investigated the potential of stingless bee honey (SBH) to suppress lipopolysaccharide (LPS)-induced systemic acute inflammation in rats and to reveal the probable mechanism of action.

Methods: Rats received 4.6 and 9.2 g/kg SBH for 7 days followed by a single injection of LPS and samples were collected after 6 h.

Results: LPS induced liver, kidney, heart and lung injury manifested by increased serum transaminases, alkaline phosphatase, creatine kinase, creatinine and urea, along with multiple histological alterations, particularly, leukocyte infiltrations. Pro-inflammatory cytokines were elevated in serum, and NF-κB p65, p38 MAPK and HMGB-1 were significantly increased in different tissues of LPS-challenged rats. SBH prevented tissue injury, ameliorated pro-inflammatory cytokines, and suppressed NF-κB p65, p38 MAPK and HMGB-1 in rats received LPS. In addition, SBH diminished reactive oxygen species (ROS) production, lipid peroxidation and oxidative DNA damage, and enhanced glutathione and Nrf2 in LPS-induced rats Conclusion: SBH prevents systemic acute inflammation by suppressing NF-κB, p38 MAPK, HMGB-1, oxidative stress and tissue injury in rats. Thus, SBH may represent an effective anti-inflammatory nutraceutical, pending further mechanistic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1386207323999200918152111DOI Listing
September 2020

Effect of visnagin on altered steroidogenesis and spermatogenesis, and testicular injury induced by the heavy metal lead.

Comb Chem High Throughput Screen 2020 Sep 18. Epub 2020 Sep 18.

Immunology Section, Department of Microbiology, College of Medicine, Taif University, Taif 21974. Saudi Arabia.

Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated.

Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation.

Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks and blood and testes samples were collected.

Results: Pb intoxication impaired the pituitary-testicular axis (PTA) manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2.

Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1386207323999200918124639DOI Listing
September 2020

Consequences of various housing systems and dietary supplementation of thymol, carvacrol, and euganol on performance, egg quality, blood chemistry, and antioxidant parameters.

Poult Sci 2020 Sep 22;99(9):4384-4397. Epub 2020 Jun 22.

Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 65211 Egypt.

The present work was carried out to investigate the influences of housing system and dietary essential oils (EOs) supplementation to laying hens on the productive performance, egg quality, immunity, antioxidant parameters, and hematology. A factorial arrangement (2 × 4) was performed, including 2 housing systems and 4 different types of EOs (without EOs, thymol, carvacrol, and euganol) during the production stages (from 28-78 wk of age). Birds were randomly divided into 2 groups with each of 2,000 birds. The first group was moved to laying cages while the second group was a floor reared. Each group was randomly divided into 4 groups (5 replicates of 100 birds each): The first were considered as a control group, and the second, third, and fourth groups were treated with thymol, carvacrol, and euganol EO, respectively. The results showed that hens reared in cage system had higher egg weight (P < 0.05), egg production, egg mass, and feed intake and better feed conversion ratio (P < 0.001) than those reared in the floor system. Blood picture values (except white blood cells), phagocytic index, phagocytic activity, and blood chemistry parameters (except calcium, phosphorus, and urea values) of laying hens were not affected (P > 0.05) by housing system. The groups fed EOs showed a rapid improvement (P < 0.001) in the egg production%, egg weight, egg mass, and egg quality. Thymol group had the highest egg production (P < 0.001). Thymol and eugenol groups had the highest egg weight, egg mass, and egg quality (P < 0.001). The groups fed diets containing thymol or eugenol consumed lower feed and had better feed conversion ratio (P < 0.001) than the control group. Immunity indices (phagocytic activity [P < 0.05], avian influenza [AIH5 and AIH9], P < 0.001) were improved with the presence of EOs in the laying hen diet. These results strongly suggest that dietary EO supplementation could be a successful attempt to improve the productive performance, egg quality, and immunity of laying hens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2020.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598024PMC
September 2020

Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats.

Environ Sci Pollut Res Int 2021 Jan 31;28(2):2019-2030. Epub 2020 Aug 31.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Liver fibrosis occurs in most types of chronic liver diseases and can develop into cirrhosis and liver failure. Bone marrow-derived mesenchymal stem cells (BMSCs) showed promising effects in the treatment of fibrosis. This study evaluated the possible role of Nrf2/HO-1 signaling in the ameliorative effect of BMSCs against carbon tetrachloride (CCl)-induced liver fibrosis, oxidative stress, and inflammation in rats. Hepatic fibrosis was induced by subcutaneous injection of CCl twice per week for 6 consecutive weeks and rat BMSCs were administered intravenously. After 4 weeks, the rats were sacrificed, and samples were collected for analysis. CCl-intoxicated rats showed elevated serum transaminases, ALP, γGT, bilirubin and pro-inflammatory cytokines, and decreased albumin. Hepatic NF-κB p65 and malondialdehyde (MDA) were significantly increased, and cellular antioxidants were decreased in CCl-intoxicated rats. BMSCs ameliorated liver function markers, suppressed MDA, NF-κB p65, and inflammatory cytokines, and enhanced antioxidants in the liver of CCl-intoxicated rats. BMSCs were engrafted within the liver tissue and prevented histological alterations and collagen accumulation induced by CCl. In addition, BMSCs upregulated hepatic Nrf2 and HO-1 expression in CCl-intoxicated rats. In conclusion, this study provides evidence that BMSCs suppress oxidative stress, inflammation, and liver fibrosis through a mechanism involving activation of the Nrf2/HO-1 signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-10637-yDOI Listing
January 2021

Flavonoids-mediated SIRT1 signaling activation in hepatic disorders.

Life Sci 2020 Oct 1;259:118173. Epub 2020 Aug 1.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Egypt. Electronic address:

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118173DOI Listing
October 2020

Evaluation of and Probiotics as Alternative Therapy for Infection in Broiler Chickens.

Animals (Basel) 2020 Jun 12;10(6). Epub 2020 Jun 12.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Chicken serovars are enteric bacteria associated with massive public health risks and economic losses. There is a widespread antimicrobial resistance among serotypes, and innovative solutions to antibiotic resistance are needed. We aimed to use probiotics to reduce antibiotic resistance and identify the major probiotic players that modify the early interactions between and host cells. One-day-old cobb broiler chicks were challenged with after oral inoculation with different probiotic strains for 3 days. The adherence of different probiotic strains to Caco-2 intestinal epithelial cells was studied in vitro. () ATTC334 and JCM1192 strains attached to Caco-2 cells stronger than BL2416. ATTC334 and JCM1192 reduced recovery from the cecal tonsils by competitive exclusion mechanism. Although BL2416 bound poorly to Caco-2 epithelial cells, it reduced recovery and increased IFN-γ and TNF-α production. ATTC334, JCM1192 and BL2416 improved body weight gain and the food conversion rate in -infected broilers. Ncc2785 neither attached to epithelial cells nor induced IFN-γ and TNF-α release and consequently did not prevent colonization in broiler chickens. In conclusion, probiotics prevented the intestinal colonization of in infected chickens by competitive exclusion or cytokine production mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10061023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341506PMC
June 2020

Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats.

Environ Sci Pollut Res Int 2020 Aug 24;27(24):30118-30132. Epub 2020 May 24.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef, Egypt.

Dyslipidemia is a risk factor for cardiovascular disease, steatohepatitis, and progression of liver disorders. This study investigated the protective effect of farnesol (FAR), a sesquiterpene alcohol, against liver injury in high cholesterol diet (HCD)-fed rats, and its modulatory effect on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). HCD was supplemented for 10 weeks, and the rats were concurrently treated with FAR. Rats that received HCD exhibited significant elevation of serum cholesterol, triacylglycerols, LDL and vLDL cholesterol, CRP, and pro-inflammatory cytokines and increased values of the cardiovascular risk indices. Serum transaminases, ALP, LDH and CK-MB, and hepatic lipid peroxidation (LPO), cholesterol, and triacylglycerols were increased in HCD-fed rats. Treatment with FAR greatly ameliorated dyslipidemia and liver function, reduced inflammatory mediators, LPO, and hepatic lipid infiltration and enhanced anti-oxidant defenses. FAR suppressed hepatic FAS, ACC, and SREPB-1c mRNA abundance and FAS activity in HDC-fed rats. In addition, molecular docking simulations pinpointed the binding modes of FAR to the active pocket residues of FAS and ACC. In conclusion, FAR possesses a strong anti-hyperlipidemic/anti-hypercholesterolemic activity mediated through its ability to modulate hepatic FAS, ACC, and SREPB-1c. FAR prevented oxidative stress, inflammation, and liver injury induced by HCD. Thus, FAR may represent a promising lipid-lowering agent that can protect against dyslipidemia and its linked metabolic deregulations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-09296-wDOI Listing
August 2020

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway.

Oxid Med Cell Longev 2020 22;2020:1675957. Epub 2020 Apr 22.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Egypt.

The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-B. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1675957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196981PMC
February 2021

Inflammasome Activation in Bovine Peripheral Blood-Derived Macrophages Is Associated with Actin Rearrangement.

Animals (Basel) 2020 Apr 10;10(4). Epub 2020 Apr 10.

Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Inflammation is critical for infection control and acts as an arsenal defense mechanism against invading microbes through activation of the host immune system. It works via its inflammasome components to sense the dangerous invading microorganism and send messages to the immune system to destroy them. To date, the function of bovine macrophage inflammasome and its relationship with actin has not been identified. This study aimed to investigate the activation of bovine inflammasome by phase one flagellin from and its interaction with actin. Bovine monocyte-derived macrophages were prepared and challenged with SL1344 phase one flagellin. The results demonstrated the relationship between the flagellin-based activation of inflammasome and actin rearrangement. The flagellin-based activation of inflammasome promoted the activation and co-localization of F-actin and the inflammasome complex. Actin was remodeled to different degrees according to the stage of inflammasome activation. The actin redistribution varied from polymerization to filopodia, while at the stage of pyroptotic cell death, actin was broken down and interacted with activated inflammasome complexes. In conclusion, flagellin-dependent inflammasome activation and actin localization to the inflammasome at the stage of pyroptotic cell death may be of importance for appropriate immune responses, pending further studies to explore the exact cross-linking between the inflammasome complex and actin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani10040655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223366PMC
April 2020

Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling.

Environ Sci Pollut Res Int 2020 Jun 3;27(17):20725-20735. Epub 2020 Apr 3.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

Chicoric acid (CA) is a natural antioxidant with promising hepatoprotective activity. We investigated the potential of CA to prevent methotrexate (MTX) hepatotoxicity, pointing to the role of Nrf2/HO-1 signaling and PPARγ. Rats received CA for 15 days and were then injected with MTX at day 16. Blood and tissue samples were collected for analysis at day 19. CA ameliorated liver function markers and mitigated histological alterations in MTX-induced rats. Pre-treatment with CA suppressed reactive oxygen species and lipid peroxidation and enhanced antioxidants in MTX-induced rats. Moreover, CA upregulated hepatic Nrf2, HO-1, NQO-1, and PPARγ, and attenuated inflammation. Consequently, CA inhibited apoptosis by increasing Bcl-2 expression and suppressing Bax, cytochrome c, and caspase-3 in MTX-administered rats. In conclusion, CA prevented oxidative stress, inflammation, and liver injury induced by MTX by activating Nrf2 /HO-1 signaling and PPARγ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-08557-yDOI Listing
June 2020

Rumex dentatus L. phenolics ameliorate hyperglycemia by modulating hepatic key enzymes of carbohydrate metabolism, oxidative stress and PPARγ in diabetic rats.

Food Chem Toxicol 2020 Apr 19;138:111202. Epub 2020 Feb 19.

Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.

Rumex dentatus L. is a flowering plant with promising therapeutic effects. This study investigated the antioxidant efficacy of phenolic compounds isolated from R. dentatus L. in vitro and by conducting density function theory (DFT) studies to explore the mechanisms of action. The antioxidant, anti-inflammatory and antidiabetic effects of polyphenols-rich R. dentatus extract (RDE) were investigated in type 2 diabetic rats. Phytochemical investigation of the aerial parts of R. dentatus resulted in the isolation of one new and seven known compounds isolated for the first time from this species. All isolated phenolics showed in vitro radical scavenging activity. The antioxidant activity of the compounds could be oriented by the hydrogen atom transfer and sequential proton loss electron transfer mechanisms in gas and water phases, respectively. In diabetic rats, RDE attenuated hyperglycemia, insulin resistance and liver injury and improved carbohydrate metabolism. RDE suppressed oxidative stress and inflammation and upregulated PPARγ. In silico molecular docking analysis revealed the binding affinity of the isolated compounds toward PPARγ. In conclusion, the computational calculations were correlated with the in vitro antioxidant activity of R. dentatus derived phenolics. R. dentatus attenuated hyperglycemia, liver injury, inflammation and oxidative stress, improved carbohydrate metabolism and upregulated PPARγ in diabetic rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111202DOI Listing
April 2020

Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats.

Antioxidants (Basel) 2020 Feb 16;9(2). Epub 2020 Feb 16.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9020159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070570PMC
February 2020

Perinatal Exposure to Tartrazine Triggers Oxidative Stress and Neurobehavioral Alterations in Mice Offspring.

Antioxidants (Basel) 2020 Jan 8;9(1). Epub 2020 Jan 8.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

The use of synthetic azo dyes as coloring agents in food products has dramatically increased. This study evaluated the effect of perinatal exposure to tartrazine (TZ) on mice offspring, focusing on neurobehavioral alterations and oxidative stress. The female mice received TZ (2.5 and 5 mg/kg) via oral gavage during pregnancy and the first 15 days after birth. At days 21 and 35 after birth, male mice were sacrificed, and samples were collected for analyses. Perinatal exposure to TZ triggered tissue injury evidenced by the histological alterations and neuronal damage in the cerebrum, medulla oblongata, and cerebellum. TZ provoked lipid peroxidation and diminished cellular antioxidants in different brain regions of the newborns. In addition, TZ increased hemoglobin content, as well as erythrocytes, leukocytes, and platelets count at days 21 and 35 after birth. Both the locomotor behavior and anxiety reflex were significantly altered in mice exposed to TZ. In conclusion, perinatal exposure to TZ within an adequate daily intake range induced oxidative stress and neurobehavioral and hematological alterations in mice offspring. Therefore, consuming foods containing TZ during pregnancy and lactation warrants public awareness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9010053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023231PMC
January 2020

Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats.

Environ Sci Pollut Res Int 2020 Mar 31;27(8):7910-7921. Epub 2019 Dec 31.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.

Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy; however, its effect against MTX hepatotoxicity remains unexplored. This study investigated the role of FA in modulating oxidative stress, inflammation, Nrf2/HO-1 signaling, and PPARγ in MTX-administered rats. Following oral FA supplementation for 15 days, rats received a single dose of MTX at day 16 and samples were collected at day 19. MTX provoked multiple histological manifestations, including degenerative changes, steatosis, inflammatory cells infiltration and hemorrhage, and altered serum transaminases, bilirubin, and albumin. Reactive oxygen species, lipid peroxidation, and nitric oxide were increased in the liver of rats that received MTX. FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats. FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3, whereas increased Bcl-2, Nrf2, NQO1, HO-1, and PPARγ. In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-019-07532-6DOI Listing
March 2020

Consumption of Terpenoids-Rich Extract Attenuates Hyperglycemia, Insulin Resistance and Oxidative Stress, and Upregulates PPARγ in a Rat Model of Type 2 Diabetes.

Antioxidants (Basel) 2019 Dec 26;9(1). Epub 2019 Dec 26.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Seaweeds are rich in structurally diverse bioactive compounds with promising therapeutic effects. This study aimed to isolate and identify terpenes from the brown alga and to investigate its antidiabetic activity, pointing to the possible involvement of peroxisome proliferator-activated receptor (PPAR)γ. Type 2 diabetes was induced by feeding rats a high fat diet (HFD) for 4 weeks followed by injection of 35 mg/kg streptozotocin (STZ). The diabetic rats received extract (PPE; 50, 100 and 200 mg/kg) for 4 weeks and samples were collected for analyses. HFD/STZ-induced rats showed hyperglycemia, dyslipidemia, impaired glucose tolerance, decreased insulin, and increased HbA1c and HOMA-IR. PPE ameliorated hyperglycemia and dyslipidemia, and improved glucose tolerance and insulin sensitivity in diabetic rats. Treatment with PPE increased hepatic hexokinase activity and glycogen, suppressed glucose-6-phosphatase, fructose-1,6-biphosphatase, and glycogen phosphorylase, and attenuated oxidative stress, inflammation, and liver injury and lipid infiltration in HFD/STZ-induced rats. In addition, PPE boosted antioxidants and upregulated PPARγ gene and protein expression in the liver of diabetic rats. Phytochemical investigation resulted in the isolation of six terpenes from PPE and in silico analysis revealed their binding affinity toward PPARγ. In conclusion, -derived terpenes attenuated hyperglycemia, dyslipidemia, oxidative stress, and inflammation, and improved insulin sensitivity and carbohydrate metabolism in type 2 diabetic rats. These beneficial effects are mediated via PPARγ activation. However, further studies to explore the exact mechanisms underlying the antidiabetic effect of PPE are recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9010022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022299PMC
December 2019

Use of as a Biomonitor of Heavy Metal Contamination from Mining Activities in Riyadh (Saudi Arabia).

Animals (Basel) 2019 Nov 29;9(12). Epub 2019 Nov 29.

Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Environmental pollution with heavy metals (HMs) is of serious ecological and public health concern worldwide. Mining is one of the main sources of HMs and can impact the environment, species diversity, and human health. This study assessed the value of as a biomonitor of environmental contamination with metal(loid)s caused by mining activities. was collected from a gold mining site and a reference site, and metal(loid)s and biochemical parameters were determined. Lead, cadmium, mercury, vanadium, arsenic, copper, zinc, and iron were significantly increased in the liver, kidney, and lung of from the mining site. Serum transaminases, alkaline phosphatase, creatinine, and urea were significantly elevated in from the mining site. Lipid peroxidation and nitric oxide were increased, whereas glutathione and antioxidant enzymes were diminished in the liver and kidney of from the mining site. In addition, multiple histological alterations were observed in the liver, kidney, and lung of . In conclusion, mining activities provoke the accumulation of metal(loid)s, oxidative stress, and tissue injury in . Therefore, is a valuable biomonitor of environmental pollution caused by mining activities and could be utilized in epidemiological avian studies of human health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani9121046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941054PMC
November 2019

Root Extract Prevents Lead-Induced Liver Injury by Attenuating Oxidative Stress and Inflammation, and Activating Akt/GSK-3β Signaling.

Antioxidants (Basel) 2019 Nov 24;8(12). Epub 2019 Nov 24.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

L () is a popular medicinal plant with promising hepatoprotective activity. This study investigated the protective effect of root extract (ALRE) on lead (Pb) hepatotoxicity, pointing to its ability to modulate oxidative stress, inflammation, and protein kinase B/Akt/glycogen synthase kinase (GSK)-3β signaling. Rats received 50 mg/kg lead acetate (Pb(Ac)) and 200 mg/kg ALRE or vitamin C (Vit. C) for 7 days, and blood and liver samples were collected. Pb(Ac) provoked hepatotoxicity manifested by elevated serum transaminases and lactate dehydrogenase, and decreased total protein. Histopathological alterations, including distorted lobular hepatic architecture, microsteatotic changes, congestion, and massive necrosis were observed in Pb(II)-induced rats. ALRE ameliorated liver function and prevented all histological alterations. Pb(II) increased hepatic lipid peroxidation (LPO), nitric oxide (NO), caspase-3, and DNA fragmentation, and serum C-reactive protein, tumor necrosis factor-α, and interleukin-1β. Cellular antioxidants, and Akt and GSK-3β phosphorylation levels were decreased in the liver of Pb(II)-induced rats. ALRE ameliorated LPO, NO, caspase-3, DNA fragmentation and inflammatory mediators, and boosted antioxidant defenses in Pb(II)-induced rats. In addition, ALRE activated Akt and inhibited GSK-3β in the liver of Pb(II)-induced rats. In conclusion, ALRE inhibits liver injury in Pb(II)-intoxicated rats by attenuating oxidative injury and inflammation, and activation of Akt/GSK-3β signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox8120582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943639PMC
November 2019

Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway.

Biomolecules 2019 11 5;9(11). Epub 2019 Nov 5.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom9110703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920970PMC
November 2019

Curcumin and Selenium Prevent Lipopolysaccharide/Diclofenac-Induced Liver Injury by Suppressing Inflammation and Oxidative Stress.

Biol Trace Elem Res 2020 Jul 25;196(1):173-183. Epub 2019 Oct 25.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.

Diclofenac (DCL), an anti-inflammatory drug used to reduce pain and inflammation, ranks in the top causes of drug-induced liver injury. The inflammatory stress induced by inflammagens is implicated in DCL-induced liver injury. Curcumin (CUR) and selenium (Se) possess anti-inflammatory effects; therefore, this study evaluated their protective potential against lipopolysaccharide (LPS)/DCL-induced liver injury. Rats received CUR and/or Se for 7 days followed by a single intravenous administration of LPS 2 h before a single injection of DCL and two other doses of CUR and/or Se 2 and 8 h after DCL. Administration of nontoxic doses of LPS and DCL resulted in liver damage evidenced by the significantly elevated liver function markers in serum. LPS/DCL-induced liver injury was confirmed by histological alterations, increased lipid peroxidation and nitric oxide, and diminished glutathione and superoxide dismutase. CUR and/or Se prevented liver injury, histological alterations, and oxidative stress and boosted antioxidant defenses in LPS/DCL-induced rats. In addition, CUR and/or Se reduced serum C-reactive protein, liver pro-inflammatory cytokines, and the expression of TLR4, NF-κB, JNK, and p38, and upregulated heme oxygenase-1 (HO-1). In conclusion, CUR and/or Se mitigated LPS/DCL-induced liver injury in rats by suppressing TLR4 signaling, inflammation, and oxidative stress and boosting HO-1 and other antioxidants. Therefore, CUR and Se can hinder the progression and severity of liver injury during acute inflammatory episodes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-019-01910-4DOI Listing
July 2020

Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats.

Antioxidants (Basel) 2019 Sep 26;8(10). Epub 2019 Sep 26.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2'-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox8100430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827027PMC
September 2019

Mesoporous Silica Nanoparticles Trigger Liver and Kidney Injury and Fibrosis Via Altering TLR4/NF-κB, JAK2/STAT3 and Nrf2/HO-1 Signaling in Rats.

Biomolecules 2019 09 25;9(10). Epub 2019 Sep 25.

Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef 62514, Egypt.

Mesoporous silica nanoparticles (MSNs) represent a promising inorganic platform for multiple biomedical applications. Previous studies have reported MSNs-induced hepatic and renal toxicity; however, the toxic mechanism remains unclear. This study aimed to investigate MSNs-induced hepatic and nephrotoxicity and test the hypothesis that altered TLR4/MyD88/NF-κB, JAK2/STAT3, and Nrf2/ARE/HO-1 signaling pathways mediate oxidative stress, inflammation, and fibrosis induced by MSNs. Rats were administered 25, 50, 100, and 200 mg/kg MSNs for 30 days, and samples were collected for analyses. MSNs induced functional and histologic alterations, increased the levels of reactive oxygen species (ROS), lipid peroxidation and nitric oxide, suppressed antioxidants, and Nrf2/HO-1 signaling in the liver and kidney of rats. MSNs up-regulated the expression of liver and kidney TLR4, MyD88, NF-κB p65, and caspase-3 and increased serum pro-inflammatory cytokines. In addition, MSNs activated the JAK2/STAT3 signaling pathway, down-regulated peroxisome proliferator activated receptor gamma (PPARγ), and promoted fibrosis evidenced by the increased collagen expression and deposition. In conclusion, this study conferred novel information on the role of ROS and deregulated TLR4/MyD88/NF-κB, JAK2/STAT3, PPARγ, and Nrf2/ARE/HO-1 signaling pathways in MSNs hepatic and nephrotoxicity. These findings provide experimental evidence for further studies employing genetic and pharmacological strategies to evaluate the safety of MSNs for their use in nanomedicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom9100528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843412PMC
September 2019

Antihyperlipidemic and Antioxidant Effects of Extract in High-Fat Diet-Fed Rats.

Biomedicines 2019 Sep 16;7(3). Epub 2019 Sep 16.

Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia.

The present study explored the antihyperlipidemic potential of a standardized methanolic extract of () leaf (MEACL) in high-fat diet (HFD)-fed rats. The standardized MEACL was orally administered at different doses (250, 500, and 1000 mg/kg) to HFD-induced hyperlipidemic rats for five weeks. Serum lipid profile, body weight changes, body mass index (BMI), daily food intake, relative organ weight, and histology of the liver were evaluated. In addition, the effect of MEACL on HMG-CoA reductase and pancreatic lipase activities as well as hepatic and fecal lipids was demonstrated. MEACL supplementation reduced serum lipids in HFD-fed rats in a dose-dependent manner. Histopathological scores revealed that 1000 mg/kg MEACL restored the damage to liver tissue in hyperlipidemic rats. MEACL decreased the body mass index (BMI), atherogenic index, and hepatic cholesterol and triglycerides and increased fecal cholesterol and bile acids in HFD-fed rats. Also, MEACL ameliorated lipid peroxidation and improved antioxidant defenses in the liver of HFD-fed rats. Furthermore, HMG-CoA reductase and lipase were suppressed by MEACL. In conclusion, this study shows the potential effect of MEACL to ameliorate hyperlipidemia and oxidative stress in HFD-fed rats. It prevented hepatic lipid accumulation and exerted an inhibitory effect on HMG-CoA reductase and lipase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines7030072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784245PMC
September 2019

Effects of Mining Activities on in Saudi Arabia: A Biochemical and Histological Study.

Animals (Basel) 2019 Sep 7;9(9). Epub 2019 Sep 7.

Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.

Mining can impact the environment, biodiversity, and human health through direct and indirect practices. This study investigated the effects of gold mining on , in relation to organ dysfunction and redox imbalance. Soil samples, , and were collected from a site near a mining plant, and a control site. Soil and samples from the mining site showed significantly higher cadmium (Cd), copper (Cu), mercury (Hg), arsenic (As), zinc (Zn), lead (Pb), and vanadium (V) levels. Hepatic, renal, and pulmonary Cd, Pb, Hg, Zn, Cu, Fe, As, and V concentrations were significantly higher in from the mining site. Markers of liver and kidney function were elevated in serum, and several histological manifestations were observed in the liver, kidney, and lung of from the mining site. Malondialdehyde and nitric oxide levels increased, and glutathione and antioxidant enzymes decreased in the liver and kidney of . In conclusion, mining practices trigger tissue damage and oxidative stress in that live close to the mining site. These findings can represent a scientific basis for evaluating the environmental and health impacts of mining on nearby communities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani9090664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770580PMC
September 2019

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity.

Biomolecules 2019 08 5;9(8). Epub 2019 Aug 5.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt.

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom9080346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723184PMC
August 2019