Sanaa M. Abd El-Twab

Improvement of lipid profile and antioxidant of hypercholesterolemic albino rats by polysaccharides extracted from the green alga Ulva lactuca Linnaeus.

Sulfated polysaccharides from Ulva lactuca were extracted in hot water and precipitated by ethanol then orally gavaged to rats fed on a hypercholesterolemic diet for 21 days to evaluate the antihypercholesterolemic and antioxidant actions. Atorvastatine Ca (Lipitor) was used as a reference drug. The intragastric administration of U. lactuca extract to hypercholesterolemic rats caused significant decrease of serum total lipids, triglycerides, total cholesterol, LDL-cholesterol and vLDL-cholesterol levels. Whereas, HDL-cholesterol concentration was markedly increased by 180%. Aqueous extract showed a significant ameliorative action on elevated atherogenic index, creatine kinase and lactate dehydrogenase activities of hypercholesterolemic group. Furthermore, serum activities of transaminases and alkaline phosphatase were also improved. High fat diet intake caused a highly significantly elevated serum urea, creatinine concentration. These effects were reversed by oral administration of U. lactuca extract. Sulfates polysaccharides extract of U. lactuca ameliorate hepatic enzymatic (catalase, glutathione peroxidase and superoxide dismutase), non-enzymatic (reduced glutathione & total thiol) antioxidant defenses and thiobarbituric acid reactive substances. In conclusion, the tested U. lactuca polysaccharides extract has potent hypocholesterolemic and antioxidant effects in experimentally-induced hypercholesterolemic animal model.

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

Abstract 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.

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

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.

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

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.

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

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/kgK2CrO4 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.

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

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.