Khan Sara A, Priyamvada Shubha, Farooq Neelam, Khan Sheeba, Khan Md Wasim, Yusufi Ahad N K
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.
Pharmacol Res. 2009 Apr;59(4):254-62. doi: 10.1016/j.phrs.2008.12.009. Epub 2009 Jan 20.
Gentamicin (GM) is an effective aminoglycoside antibiotic against severe infections but nephrotoxicity and oxidative damage limits its long term clinical use. Various strategies were attempted to ameliorate GM nephropathy but were not found suitable for clinical practice. Green tea (GT) polyphenols have shown strong chemopreventive and chemotherapeutic effects against various pathologies. We hypothesized that GT prevents GM nephrotoxicity by virtue of its antioxidative properties. A nephrotoxic dose of GM was co-administered to control and GT-fed male Wistar rats. Serum parameters and enzymes of oxidative stress, brush border membrane (BBM), and carbohydrate metabolism were analyzed. GM increased serum creatinine, cholesterol, blood urea nitrogen (BUN), lipid peroxidation (LPO) and suppressed superoxide dismutase (SOD) and catalase activities in renal tissues. Activity of hexokinase, lactate dehydrogenase increased whereas malate dehydrogenase decreased. Gluconeogenic enzymes and glucose-6-phosphate dehydrogenase were differentially altered in the cortex and medulla. However, GT given to GM rats reduced nephrotoxicity parameters, enhanced antioxidant defense and energy metabolism. The activity of BBM enzymes and transport of Pi declined by GM whereas GT enhanced BBM enzymes and Pi transport. In conclusion, green tea ameliorates GM elicited nephrotoxicity and oxidative damage by improving antioxidant defense, tissue integrity and energy metabolism.
庆大霉素（GM）是一种有效的氨基糖苷类抗生素，可用于治疗严重感染，但肾毒性和氧化损伤限制了其长期临床应用。人们尝试了各种策略来改善庆大霉素肾病，但均未发现适用于临床实践。绿茶（GT）多酚已显示出对各种病症具有强大的化学预防和化学治疗作用。我们假设绿茶凭借其抗氧化特性可预防庆大霉素的肾毒性。将肾毒性剂量的庆大霉素共同给予对照大鼠和喂食绿茶的雄性Wistar大鼠。分析了氧化应激、刷状缘膜（BBM）和碳水化合物代谢的血清参数及酶。庆大霉素可增加血清肌酐、胆固醇、血尿素氮（BUN）、脂质过氧化（LPO），并抑制肾组织中的超氧化物歧化酶（SOD）和过氧化氢酶活性。己糖激酶、乳酸脱氢酶活性增加，而苹果酸脱氢酶活性降低。糖异生酶和葡萄糖-6-磷酸脱氢酶在皮质和髓质中的变化存在差异。然而，给予庆大霉素大鼠绿茶可降低肾毒性参数，增强抗氧化防御和能量代谢。庆大霉素会降低BBM酶的活性和无机磷（Pi）转运，而绿茶则可增强BBM酶活性和Pi转运。总之，绿茶通过改善抗氧化防御、组织完整性和能量代谢，减轻了庆大霉素引起的肾毒性和氧化损伤。
