title: Diosmin protects against trichloroethylene-induced renal injury in Wistar rats: plausible role of p53, Bax and caspases.
abstract: Diosmin (DM) is a naturally occurring flavone and has been found to possess numerous therapeutic properties. In this study, we used DM as a protective agent against the nephrotoxic effects of the environmental toxicant trichloroethylene (TCE). Male Wistar rats were divided into five groups (I-V, n 6). Groups II, III and IV received an oral administration of TCE at a dose of 1000 mg/kg body weight for twenty consecutive days. The animals in groups II and III received an oral treatment of DM at doses of 20 and 40 mg/kg body weight, respectively, for twenty consecutive days, while groups I and V were given maize oil (5 ml/kg body weight and DM 40 mg/kg body weight, respectively) for 20 d. The protective effects of DM on TCE-induced oxidative stress and caspase-dependent apoptosis were investigated by assaying oxidative stress biomarkers, lipid peroxidation (LPO), serum toxicity markers, alkaline unwinding assay, caspase-3, -7 and -9, Bax and p53 expression. Oral administration of TCE in rats enhanced renal LPO, depleted glutathione content and antioxidant enzymes, induced DNA strand breaks (P<0·001), modulated the expression of Bax and p53 protein and induced the expression of caspase-3, -7 and -9. Co-treatment with DM prevented oxidative stress by restoring the levels of antioxidant enzymes; furthermore, a significant dose-dependent decrease in DNA disintegration and kidney toxicity markers such as blood urea N, creatinine, lactate dehydrogenase and kidney injury molecule-1 was observed. DM also effectively decreased the TCE-induced up-regulation of Bax and p53. Data from the present study establish the protective role of DM against TCE-induced renal damage.
authors: Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110 062, India.
authors: Muneeb U
authors: MU
authors: Rehman
authors: Mir
authors: M
authors: Tahir
authors: Abdul
authors: A
authors: Quaiyoom Khan
authors: Rehan
authors: R
authors: Khan
authors: Abdul
authors: A
authors: Lateef
authors: Oday O
authors: OO
authors: Hamiza
authors: Farrah
authors: F
authors: Ali
authors: Sarwat
authors: S
authors: Sultana
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage; D019587:Dietary Supplements; D004145:Diosmin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000293:injuries; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014241:Trichloroethylene / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014241:Trichloroethylene; D004145:Diosmin; D002374:Catalase; D020169:Caspases