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丁香酚对庆大霉素诱导的大鼠肾毒性和氧化损伤的保护作用。

The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney.

机构信息

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt.

出版信息

Fundam Clin Pharmacol. 2011 Dec;25(6):708-16. doi: 10.1111/j.1472-8206.2010.00900.x. Epub 2010 Nov 24.

Abstract

Gentamicin (GM) is an effective aminoglycoside antibiotic against life-threatening Gram-negative bacteria. However, a major complication of therapeutic doses of GM is nephrotoxicity, which is believed to be related to the generation of reactive oxygen species. The present study was therefore aimed to investigate the protective effect of eugenol, a phenolic antioxidant, on GM-induced nephrotoxicity in Sprague-Dawley rats. Intramuscular injection of rats with GM (80 mg/kg body weight/day) for six consecutive days induced marked acute renal failure, manifested by a sharp significant increase in serum urea and creatinine levels, along with a significant depletion of serum potassium level, compared to normal controls. GM-induced renal dysfunction was attributable to enhanced oxidative stress, as revealed by decreased superoxide dismutase and catalase activities, glutathione depletion and increased lipid peroxidation. Furthermore, kidney lactate dehydrogenase activity, as an indicator of hypoxia, was significantly increased by GM administration. Eugenol (100 mg/kg body weight, per os) administered four days before and six days concurrently with GM (80 mg/kg body weight, i.m.) restored normal renal functions and suppressed GM-induced oxidative stress and hypoxia. Light microscopical examination of the renal tissues of GM-treated animals demonstrated severe tubular necrosis at the cortex and increased cellular inflammatory processes. However, these alterations were considerably reduced with eugenol coadministration. In conclusion, eugenol ameliorates GM-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense.

摘要

庆大霉素(GM)是一种有效的氨基糖苷类抗生素,可用于治疗危及生命的革兰氏阴性菌感染。然而,GM 的治疗剂量会引起严重的副作用,即肾毒性,这被认为与活性氧(ROS)的产生有关。因此,本研究旨在探讨丁香酚(一种酚类抗氧化剂)对 GM 诱导的 SD 大鼠肾毒性的保护作用。连续 6 天,通过肌肉注射方式给大鼠 GM(80mg/kg 体重/天),可导致明显的急性肾衰竭,表现为血清尿素和肌酐水平急剧显著升高,同时血清钾水平显著降低,与正常对照组相比差异有统计学意义。GM 引起的肾功能障碍归因于氧化应激的增强,表现为超氧化物歧化酶和过氧化氢酶活性降低、谷胱甘肽耗竭和脂质过氧化增加。此外,GM 给药可导致肾脏乳酸脱氢酶活性(缺氧的指标)显著增加。丁香酚(100mg/kg 体重,口服)在 GM(80mg/kg 体重,肌肉注射)给药前 4 天和同时给药 6 天,可恢复正常肾功能,并抑制 GM 诱导的氧化应激和缺氧。GM 处理动物的肾组织光镜检查显示皮质严重的肾小管坏死和细胞炎症过程增加。然而,这些变化在丁香酚共同给药时明显减少。总之,丁香酚通过清除自由基、减少脂质过氧化和改善细胞内抗氧化防御,改善 GM 诱导的肾毒性和氧化损伤。

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