Banday Anees A, Farooq Neelam, Priyamvada Shubha, Yusufi Ahad N K, Khan Farah
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.
Life Sci. 2008 Feb 27;82(9-10):450-9. doi: 10.1016/j.lfs.2007.11.014. Epub 2007 Dec 5.
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.
庆大霉素（GM）是一种用于治疗危及生命的细菌感染的抗生素，会对肾脏产生显著毒性。组织学研究表明，特别是肾近端曲管的线粒体、微粒体、溶酶体和质膜是GM的主要作用靶点。尽管进行了大量研究，但GM肾毒性的生化/细胞基础仍未得到充分理解。最近，活性氧（ROS）被认为是GM诱导肾毒性的重要介质。我们假设GM会对细胞内细胞器造成损伤，影响其结构完整性，并改变代谢和其他功能能力。为了验证上述假设，我们研究了GM对血液/尿液参数、碳水化合物代谢酶、刷状缘膜（BBM）和基底外侧膜（BLM）、溶酶体以及肾组织氧化应激的长期、时间依赖性影响。每天给大鼠注射肾毒性剂量的GM（80mg/kg体重），持续15天。GM的长期治疗导致血清肌酐、血尿素氮显著升高，随后出现大量蛋白尿、糖尿、酶尿以及尿液中电解质流失。碳水化合物代谢酶、质膜、溶酶体的活性显著下降。抗氧化酶如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性严重降低，肾皮质和髓质中的脂质过氧化显著增加。我们得出结论，GM给药诱导了肾组织的氧化损伤，导致碳水化合物代谢受损，BBM、BLM和溶酶体的活性降低，同时脂质过氧化物增加。
