Publications by authors named "Sanaa M Abd El-Twab"

18 Publications

  • Page 1 of 1

Prophylactic effects of Cynara scolymus L. leaf and flower hydroethanolic extracts against diethylnitrosamine/acetylaminoflourene-induced lung cancer in Wistar rats.

Environ Sci Pollut Res Int 2021 Apr 9. Epub 2021 Apr 9.

Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Salah Salem St, 62511, Beni-Suef, Egypt.

The study examines the prophylactic action of artichoke leaf hydroethanolic extract (ALE) and artichoke flower head hydroethanolic extract (AFE) against diethylnitrosamine (DEN)/acetylaminofluorene (AAF)-induced lung cancer in Wistar rats. To chemically induce lung cancer, DEN was injected intraperitoneally twice a week for a fortnight at a dose of 150 mg/kg body weight (b.w.), followed by oral supplementation of AAF four times a week for 3 weeks at a dose of 20 mg/kg b.w. The DEN/AAF-administered rats were orally supplemented with ALE or AFE at a dose of 100 mg/kg b.w. for 17 weeks starting from the 1st week of DEN injection to the 17th week of the experiment. The lung cancerous injuries resulting from DEN/AAF-administration were significantly improved by the treatment with ALE and AFE as observed in histological examination. In addition, there was a significant reduction in lung lipid peroxidation, with resultant elevation in antioxidant enzymatic activity of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and superoxide dismutase as well as glutathione content in DEN/AAF-supplemented rats treated with ALE and AFE as compared to DEN/AAF-administered control. The lung tumor suppressor protein (p53) and B-cell lymphoma-2 (Bcl-2) mRNA expression significantly increased in the rats treated with ALE and AFE. In conclusion, the finding showed that ALE and AFE produced anti-cancer prophylactic effects against DEN/AAF-induced lung cancer in rats via suppression of oxidative stress and improved apoptotic signal induction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-13391-xDOI Listing
April 2021

Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers.

Biochemistry (Mosc) 2021 Feb;86(2):179-189

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

Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1β mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1134/S0006297921020061DOI Listing
February 2021

Musa paradisiaca L. leaf and fruit peel hydroethanolic extracts improved the lipid profile, glycemic index and oxidative stress in nicotinamide/streptozotocin-induced diabetic rats.

Vet Med Sci 2021 Mar 5;7(2):500-511. Epub 2020 Dec 5.

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

This study aimed to assess antihyperlipidemic, cardiac and antioxidant effects as well as mode of actions of Musa paradisiaca (M. paradisiaca) leaf and fruit peel hydroethanolic extracts in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), 15 min after intraperitoneal injection of NA (120 mg/kg body weight). NA/STZ-induced diabetic rats were orally supplemented with M. paradisiaca leaf and fruit peel hydroethanolic extracts in a dose of 100 mg/kg body weight/day for 28 days. The treatment of NA/STZ-induced diabetic rats with M. paradisiaca leaf and fruit peel extracts significantly decreased the elevated fasting and post-prandial serum glucose, total cholesterol, triglycerides, LDL-cholesterol and vLDL-cholesterol levels and significantly increased the lowered serum insulin level, liver glycogen content, serum HDL-cholesterol level, homeostasis model assessment-insulin resistance (HOMA-IS) and HOMA-β cell function. The elevated cardiovascular risk indices in diabetic rats were significantly improved due to treatment with M. paradisiaca extracts. Concomitant with the increase in liver glycogen content, the glucose-6-phosphatase activity significantly decreased reflecting the decrease in hepatic glucose output. The heart function was potentially ameliorated as manifested by decrease in the elevated serum creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities after treatments of diabetic rats with M. paradisiaca extracts. The elevated liver lipid peroxidation and the decline in liver glutathione content and superoxide dismutase, glutathione peroxidase and glutathione-S-transferase activities were significantly reversed by treatments. Thus, it can be concluded that M. paradisiaca leaf and fruit peel hydroethanolic extracts may have antihyperlipidemic and cardioprotective potentials in NA/STZ-induced diabetic rats. These effects may be mediated via improvements in the glycemic state, β-cell function, tissue insulin sensitivity, and antioxidant defense mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/vms3.389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025632PMC
March 2021

Polydatin mitigates pancreatic β-cell damage through its antioxidant activity.

Biomed Pharmacother 2021 Jan 26;133:111027. Epub 2020 Nov 26.

Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Japan. Electronic address:

Several reports have been shown the pivotal role of oxidative stress in the progression of diabetes mellitus and its complications. Polydatin (PD), a natural phytochemical, has wide range of pharmacological actions, however, the underlying beneficial effects in pancreas was not clarified. In the current study, using in vivo and in vitro models, we investigated the possible protective effects of PD against oxidative damage in pancreatic β-cells. Diabetic rats were examined after oral administration with PD (50 mg/kg b.wt.) for 28 days. Results revealed that PD significantly enhanced glucose tolerance and insulin secretion in the bloodstream of diabetic rats as well as lipid metabolism. Interestingly, in vivo results indicated that PD decreased the lipid peroxidation, improved the antioxidant status, and inhibited the inflammation in pancreas. Alongside, we artificially induced oxidative stress by exposing the insulin-producing RINm5F cells to hydrogen peroxide in the presence or absence of PD. The co-treatment with PD preserved cell viability, reduced ROS accumulation, as well as enhanced the anti-oxidant, anti-apoptotic, and cell function markers. To conclude, PD exhibited potential action in preserving β-cell function and inhibiting oxidative damage probably through its antioxidant properties. Thus, PD could be a possible therapeutic agent for diabetic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2020.111027DOI Listing
January 2021

New insights into the , and antihyperglycemic mechanisms of gallic acid and -coumaric acid.

Arch Physiol Biochem 2020 May 13:1-7. Epub 2020 May 13.

Faculty of Pharmacy, The British University, Cairo, Egypt.

To explore the probable and mechanisms of gallic acid (GA) and -coumaric acid (PCA) as anti-hyperglycemic agents. Male albino rats were allocated into four groups, group1 was used as normal control. Group 2 was established as a diabetic control and group3 and 4 were treated with an oral dose of GA and PCA, respectively. GA and PCA revealed a significant decrease in the activity of α-amylase, a noticeable rise in glucose induced-insulin secretion and glucose-uptake in peripheral glucose-uptake , increase also liver glycogen and serum insulin levels . Further, GA and PCA exhibited a significant reduction in intestinal glucose absorption compared to blank. The antihyperglycemic activities of GA and PCA can be mediated through delaying intestinal glucose absorption, enhancing β-cell activity and promoting glucose uptake by peripheral tissue enhancing insulin sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13813455.2020.1762659DOI Listing
May 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

Antihyperglycemic Effects and Mode of Actions of Leaf and Fruit Peel Hydroethanolic Extracts in Nicotinamide/Streptozotocin-Induced Diabetic Rats.

Evid Based Complement Alternat Med 2020 26;2020:9276343. Epub 2020 Jan 26.

Biochemistry Division, Chemistry Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.

The present study aimed to evaluate the antihyperglycemic effects of () leaf and fruit peel hydroethanolic extracts and to suggest their probable mode of actions in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. The leaf and fruit peel hydroethanolic extracts were analyzed by GC-MS that indicated the presence of phytol, octadecatrienoic acid, hexadecanoic acid, and octadecadienoic acid as major components in the leaf extract and vitamin E, octadecenamide, -sitosterol, and stigmasterol as major phytochemicals in the fruit peel extract. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight) dissolved in citrate buffer (pH 4.5), 15 minutes after intraperitoneal injection of NA (120 mg/kg body weight). The NA/STZ-induced diabetic rats were, respectively, treated with . leaf and fruit peel hydroethanolic extracts at a dose of 100 mg/kg body weight/day by oral administration for 28 days. The treatment of NA/STZ-induced diabetic rats with leaf and fruit peel extracts significantly improved the impaired oral glucose tolerance and significantly increased the lowered serum insulin and C-peptide levels. The HOMA-IR (as the index of insulin resistance) and QUICKI (as a marker for insulin sensitivity), as well as HOMA- cell function were significantly alleviated as a result of treatment of diabetic rats with leaf and fruit peel extracts. In association, the elevated serum-free fatty acids, TNF-, and IL-6 levels were significantly decreased. In addition, the suppressed adipose tissue PPAR, GLUT4, adiponectin, and insulin receptor -subunit mRNA expressions were upregulated while the elevated adipose tissue resistin expression was downregulated in diabetic rats as a result of treatment with the leaf and peel extract. Based on these results, it can be concluded that leaf and fruit peel hydroethanolic extracts have antihyperglycemic effects which may be mediated via their insulinotropic and insulin-sensitizing effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9276343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007756PMC
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

Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis.

Food Funct 2019 Aug 10;10(8):4593-4607. Epub 2019 Jul 10.

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

Drug-induced nephrotoxicity contributes to acute kidney injury (AKI) and represents a major problem in the clinical setting. We investigated the possible involvement of NLRP3 inflammasome activation in methotrexate (MTX)-induced nephrotoxicity and the protective potential of ferulic acid (FA), pointing out the role of PPARγ and Nrf2/HO-1 signaling. Rats that received MTX showed a significant increase in circulating creatinine and urea, and kidney Kim-1 levels along with multiple histological alterations. Reactive oxygen species (ROS), malondialdehyde and nitric oxide levels showed a significant increase in the kidney of rats that received MTX, while antioxidant defenses were diminished. FA ameliorated kidney function markers, prevented histological alterations, suppressed ROS production and enhanced antioxidant defenses. FA inhibited MTX-induced inflammasome activation as showed by the decreased phosphorylation of NF-κB, and expression of NLRP3, caspase-1 and IL-1β. MTX caused apoptosis marked by increased expression of BAX, cytochrome c and caspase-3, and suppressed Bcl-2, effects that were significantly reversed in FA-treated groups. In addition, FA up-regulated Nrf2/ARE/HO-1 signaling and PPARγ expression in the kidney of MTX-induced rats. In conclusion, activation of NLRP3 inflammasome may represent a new mechanism for MTX nephrotoxicity. FA up-regulated PPARγ and Nrf2 signaling, prevented overproduction of ROS, and suppressed NF-κB/NLRP3 inflammasome axis and apoptosis in the kidney of MTX-induced rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9fo00114jDOI Listing
August 2019

Chicoric acid prevents methotrexate-induced kidney injury by suppressing NF-κB/NLRP3 inflammasome activation and up-regulating Nrf2/ARE/HO-1 signaling.

Inflamm Res 2019 Jun 29;68(6):511-523. Epub 2019 Apr 29.

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

Objective: Chicoric acid (CA) is a natural product with promising antioxidant and anti-inflammatory properties; however, its protective effect on methotrexate (MTX)-induced acute kidney injury (AKI) hasn't been reported. We investigated the effect of CA on MTX-induced AKI in rats, pointing to the role of NF-κB/NLRP3 inflammasome and Nrf2/ARE/HO-1 signaling.

Materials And Methods: Wistar rats received 25 mg/kg and 50 mg/kg CA for 15 days and a single injection of MTX at day 16. At day 19, the rats were killed, and samples were collected for analyses.

Results: MTX induced a significant increase in serum creatinine and urea, and kidney Kim-1, reactive oxygen species (ROS), malondialdehyde and nitric oxide levels. In addition, MTX-induced rats exhibited multiple histopathological alterations, diminished antioxidant defenses, and decreased expression of Nrf2, NQO-1 and HO-1. CA prevented histological alterations, ameliorated kidney function markers, attenuated ROS production and lipid peroxidation, and boosted antioxidant defenses. CA suppressed the expression of NF-κB p65, NLRP3, caspase-1 and IL-1β in the kidney of MTX-induced rats. Furthermore, CA inhibited MTX-induced apoptosis as evidenced by the decreased expression of BAX and caspase-3, and increased Bcl-2 gene expression.

Conclusions: CA prevented MTX-induced AKI through activation of Nrf2/ARE/HO-1 signaling, and attenuation of ROS-induced activation of NF-κB/NLRP3 inflammasome signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00011-019-01241-zDOI Listing
June 2019

Modulation of hyperglycemia and dyslipidemia in experimental type 2 diabetes by gallic acid and p-coumaric acid: The role of adipocytokines and PPARγ.

Biomed Pharmacother 2018 Sep 20;105:1091-1097. Epub 2018 Jun 20.

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

There are many indications that confirm the vital role of adipocytokines and PPARγ in diabetics. Hence, the current investigation aimed to study the modulatory effects of gallic acid and p-coumaric acid on adipocytokines secretion and PPARγ mRNA expression in type 2 diabetic rats. After induction of type 2 diabetes, diabetic rats were orally treated with 20 mg/kg body mass gallic acid and 40 mg/kg body mass p-coumaric acid for six weeks. Among treatment diabetic rats, glucose and glycosylated hemoglobin levels significantly declined in diabetic rats, while insulin level and body weight significantly increased as compared to control group. Gallic acid and p-coumaric acid markedly decreased the level of TNF-α and increased the levels of PPARγ mRNA and adiponectin. In addition, the tested agents improved markedly lipid profile parameters, cardiovascular indices 1 and 2 and anti-atherogenic index. In conclusion, gallic acid and p-coumaric acid exhibited marked antidiabetic action that could be mediated via modulation of TNF-α and adipocytokines secretions as well as upregulation of PPARγ mRNA expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.06.096DOI Listing
September 2018

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

Metab Brain Dis 2017 08 2;32(4):1279-1286. Epub 2017 Jun 2.

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

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11011-017-0039-8DOI Listing
August 2017

Caffeic acid phenethyl ester protects the brain against hexavalent chromium toxicity by enhancing endogenous antioxidants and modulating the JAK/STAT signaling pathway.

Biomed Pharmacother 2017 Jul 2;91:303-311. Epub 2017 May 2.

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

Hexavalent chromium [Cr(VI)] is commonly used in industry, and is a proven toxin and carcinogen. However, the information regarding its neurotoxic mechanism is not completely understood. The present study was designed to scrutinize the possible protective effects of caffeic acid phenethyl ester (CAPE), a bioactive phenolic of propolis extract, on Cr(VI)-induced brain injury in rats, with an emphasis on the JAK/STAT signaling pathway. Rats received 2mg/kgKCrO and concurrently treated with 20mg/kg CAPE for 30 days. Cr(VI)-induced rats showed a significant increase in cerebral lipid peroxidation, nitric oxide and pro-inflammatory cytokines, with concomitantly declined antioxidants and acetylcholinesterase. CAPE attenuated oxidative stress and inflammation and enhanced antioxidant defenses in the cerebrum of rats. Cr(VI) significantly up-regulated JAK2, STAT3 and SOCS3, an effect that was reversed by CAPE. In conclusion, CAPE protects the brain against Cr(VI) toxicity through abrogation of oxidative stress, inflammation and down-regulation of JAK2/STAT3 signaling in a SOCS3-independent mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2017.04.073DOI Listing
July 2017

Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPARγ and Nrf2: Protective effect of 18β-Glycyrrhetinic acid.

Chem Biol Interact 2017 May 13;270:59-72. Epub 2017 Apr 13.

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

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice with promising hepatoprotective activity. However, its protective mechanism on methotrexate (MTX) hepatotoxicity in not well defined. We investigated the hepatoprotective effect of 18β-GA, pointing to the role of peroxisome proliferator activated receptor gamma (PPARγ) and the redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered 18β-GA (50 and 100 mg/kg) 7 days either before or after MTX injection. MTX induced significant increase in circulating liver function marker enzymes and bilirubin with concomitant declined albumin levels. Serum pro-inflammatory cytokines, and liver malondialdehyde and nitric oxide were significantly increased in MTX-induced rats. Treatment with 18β-GA significantly reduced serum enzymes of liver function, bilirubin and pro-inflammatory cytokines. 18β-GA attenuated MTX-induced oxidative stress and restored the antioxidant defenses. In addition, 18β-GA improved liver histological structure and decreased the expression of Bax whereas increased Bcl-2 expression. MTX-induced rats showed significant down-regulation of Nrf2, hemoxygenase-1 and PPARγ, an effect that was markedly reversed by 18β-GA supplemented either before or after MTX. In conclusion, 18β-GA protected against MTX-induced liver injury, possibly by activating Nrf2 and PPARγ, and subsequent attenuation of inflammation, oxidative stress and apoptosis. Therefore, 18β-GA can provide protection against MTX-induced hepatotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2017.04.009DOI Listing
May 2017

Gallic acid attenuates chromium-induced thyroid dysfunction by modulating antioxidant status and inflammatory cytokines.

Environ Toxicol Pharmacol 2016 Dec 27;48:225-236. Epub 2016 Oct 27.

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

Hexavalent chromium-mediated oxidative stress causes severe organ damage. The present study was designed to investigate the possible thyroprotective effect and underlying mechanisms of gallic acid using rat model of potassium dichromate-induced thyroid dysfunction. Forty adult male albino rats were divided into 4 groups: control, gallic acid (20mg GA/kg b. wt), potassium dichromate (2mg PD/kg b. wt) and the fourth group was co-treated with PD and GA. PD-injection resulted in decreased serum free triiodothyonine (FT3), free thyroxine (FT4) with concomitant significant increase in thyroid stimulating hormone (TSH) levels. Superoxide dismutase (SOD), glutathione-S-transferase (GST) activities and their respective mRNA expression and reduced glutathione (GSH) content were significantly decreased. Thyroid nitrosative stress marker (NO level and iNOS mRNA and protein expression) and pro-inflammatory cytokines (serum TNF-α, IL-6 and thyroid TNF-α, IL-6 and COX-2 gene and protein expression levels) were disturbed. Histopathological changes revealed distended, collapsed and degenerated follicles with vacuolated cytoplasm. GA co-treatment attenuated pro-inflammatory cytokines, the thyroid expression of iNOS, TNF-α, IL-6 and COX-2, decreased the elevated lipid peroxidation biomarkers and NO level and up- regulated SOD and GST mRNA expression levels. In conclusion, GA has shown strong modulatory potential against PD-induced inflammation and oxidative stress in albino rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2016.08.019DOI Listing
December 2016

18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants.

Ren Fail 2016 Oct 8;38(9):1516-1527. Epub 2016 Aug 8.

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

Objectives: 18β-glycyrrhetinic acid (18β-GA) has multiple beneficial and therapeutic effects. However, its protective roles on methotrexate (MTX)-induced renal injury are not well defined. In the present study, we investigated the possible protective effects of 18β-GA against MTX-induced nephrotoxicity in rats.

Materials: 18β-GA (50 and 100 mg/kg) was administered for 7 days either before or after MTX. The rats were decapitated and kidney and serum samples were collected.

Results: MTX-induced renal injury in rats was evidenced by the significant (p < 0.001) increase in circulating kidney function markers and tumor necrosis factor alpha (TNF-α), as well as the histopathological alterations. MTX-induced rats exhibited significantly increased lipid peroxidation (p < 0.05) and nitric oxide (p < 0.001) levels, with concomitant marked (p < 0.001) decline in the antioxidant defenses. 18β-GA, administered either before or after MTX, produced a significant amelioration of circulating kidney function markers, TNF-α, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In addition, 18β-GA supplementation significantly up-regulated the mRNA abundance of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO-1) in the kidney of MTX-induced rats.

Conclusions: These results indicate that 18β-GA has a protective effect on MTX-induced nephrotoxicity with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling. These findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2016.1216722DOI Listing
October 2016

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

Can J Physiol Pharmacol 2016 Jun 19;94(6):651-61. Epub 2016 Jan 19.

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

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P < 0.001) increase in glycosylated hemoglobin, glucose, homeostasis model of insulin resistance, and pro-inflammatory cytokines. Serum insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly (P < 0.001) decreased in diabetic rats. Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P < 0.001) down-regulated in testes of diabetic rats, an effect which was significantly increased after administration of taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/cjpp-2015-0503DOI Listing
June 2016

Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.

Eur J Nutr 2017 Jun 8;56(4):1671-1684. Epub 2016 Apr 8.

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

Purpose: Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated.

Methods: Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks.

Results: Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina.

Conclusion: These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-016-1214-0DOI Listing
June 2017