Papers by Hesham El-Beshbishy
European Journal of Pharmacology, 2011
Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utili... more Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of present study is to investigate biochemical and molecular effects of alpha lipoic acid (ALA) to protect against cisplatin-induced nephrotoxicity in mice. Cisplatin (12 mg/kg/day) was administered i.p. for 4 days. Group of mice were given ALA (20 mg/kg/day) for 18 days. Another set were administered ALA for 4 days before and 14 days after cisplatin intoxication. The results obtained revealed that kidney/body weight ratio of cisplatin-treated mice was increased by +40%. ALA intake declined the ratio by -19%. Serum creatinine and urea levels were increased in cisplatin-treated mice by +375% and +69%, respectively. These changes were moved to normalcy upon ALA intake. Cisplatin treatment elevated malondialdehyde (MDA) by 27 fold and declined reduced glutathione (GSH) by -49%. Cisplatin decreased catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes by -47%, -49% and -59%, respectively. ALA decreased the MDA by -286% and increased the GSH, catalase, SOD and GPx levels by +60%, +81%, +90% and +38%, respectively. ALA increased mRNA expression of catalase, CuZn SOD and GPx genes near to normalcy compared to cisplatin-treated mice. Cisplatin-treated mice increased caspase-3-activity by +223%, nitric oxide (NO) by +74% and inducible nitric oxide synthase (iNOS) by 10 fold. ALA intake declined these changes by -43%, -45% and -73%, respectively. ALA may play renoprotective role on cisplatin-induced nephrotoxicity through antioxidant and antiapoptotic mechanisms combined with initiation of mRNA expression of antioxidant genes.
Toxicology and Industrial Health, 2012
Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the p... more Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in manufacturing plastic baby bottles and lining of food cans. In this study, we investigated the BPA-induced testicular oxidative stress and perturbation of mitochondrial marker enzymes in male albino rats and its amelioration by α-lipoic acid (LA). Rats were administered a dose of BPA (10 mg/kg body weight) orally for 14 days. This resulted in decreased testes weight, total testicular protein content, testicular enzymes such as acid phosphatase, alkaline phosphatase and lactate dehydrogenase and decline in activities of marker mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, monoamine oxidase and NADH dehydrogenase. The serum testosterone and total antioxidant status were reduced. Besides, it also affected the activities of testicular antioxidant enzymes such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. BPA also caused lipid peroxidation and decrease in reduced glutathione content of mitochondria. The co-administration of LA (20 mg/kg body weight; orally for 14 days) together with BPA resulted in restoration of the mitochondrial marker enzyme activities and increasing enzymatic and non-enzymatic antioxidants of mitochondria. The obtained results demonstrated that LA has a potential role in mitigating BPA-induced mitochondrial toxicity through antioxidant mechanism or by direct free radical scavenging activity.
Fundamental & clinical pharmacology, 2013
Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen s... more Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and th...
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Papers by Hesham El-Beshbishy