title: Time dependent effects of gentamicin on the enzymes of carbohydrate metabolism, brush border membrane and oxidative stress in rat kidney tissues.
abstract: Gentamicin (GM), an antibiotic against life threatening bacterial infection, induces remarkable toxicity in the kidney. Histological studies have indicated that mitochondria, microsomes, lysosomes and plasma membranes of renal proximal convoluted tubules in particular are major GM targets. Despite numerous investigations, the biochemical/cellular basis of GM nephrotoxicity is not well understood. Recently reactive oxygen species (ROS) are considered to be important mediators of GM-induced nephrotoxicity. We hypothesize that GM causes damage to intracellular organelles and affects their structural integrity and alters metabolic and other functional capabilities. To address above hypothesis a long-term, time-dependent effect of GM has been studied on blood/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM) and basolateral (BLM), lysosomes and oxidative stress in renal tissues. A nephrotoxic dose of GM (80 mg/kg body weight) was administered to rats daily for 15 days. The long-term treatment with GM induced a significant increase in serum creatinine, blood urea nitrogen followed by massive proteinuria, glucosuria, enzymuria along with loss of electrolytes in the urine. The activities of the enzymes of carbohydrate metabolism, plasma membranes, lysosomes significantly declined. The activities of antioxidant enzymes e.g. superoxide dismutase, catalase and glutathione peroxidase were severely depressed and lipid peroxidation was significantly increased in the renal cortex and medulla. We conclude that GM administration induced oxidative damage to renal tissues that resulted in impaired carbohydrate metabolism and decreased activities of BBM, BLM and lysosomes associated with increased lipid peroxides.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
authors.forename: Anees A
authors.initials: AA
authors.lastname: Banday
authors.forename: Neelam
authors.initials: N
authors.lastname: Farooq
authors.forename: Shubha
authors.initials: S
authors.lastname: Priyamvada
authors.forename: Ahad N K
authors.initials: AN
authors.lastname: Yusufi
authors.forename: Farah
authors.initials: F
authors.lastname: Khan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000652:urine; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood / Q000652:urine; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008315:Malondialdehyde; D012964:Sodium; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D011188:Potassium