Oktem Faruk, Arslan Meltem Koyuncu, Ozguner Fehmi, Candir Ozden, Yilmaz H Ramazan, Ciris Metin, Uz Efkan
Department of Pediatric Nephrology, Suleyman Demirel University, School of Medicine, Isparta, Turkey.
Toxicology. 2005 Nov 15;215(3):227-33. doi: 10.1016/j.tox.2005.07.009. Epub 2005 Aug 19.
The aims of this study were to examine vancomycin (VCM)-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM-induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i.p.) with 200mgkg(-1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM-induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels.
本研究的目的是检测万古霉素（VCM）诱导的促进活性氧（ROS）生成的氧化应激，并研究祛痰剂厄多司坦（erdosteine）在大鼠肾脏组织中对VCM可能诱导的肾损伤的作用，厄多司坦也具有抗氧化特性。大鼠被分为三组：假手术组、VCM组和VCM加厄多司坦组。VCM以200mg/kg（-1）的剂量腹腔注射（i.p.），每日两次，共7天。厄多司坦经口给药。对对照大鼠给予VCM显著增加了肾丙二醛（MDA）和尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG，肾小管损伤标志物）排泄，但降低了超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。与单独使用VCM相比，VCM注射同时给予厄多司坦导致肾MDA和尿NAG排泄显著降低，SOD活性增加，但肾组织中的CAT活性未增加。厄多司坦对VCM诱导的肾毒性具有组织病理学保护作用。与对照组和厄多司坦组相比，VCM处理的大鼠肾小管腔明显扩张，广泛的上皮细胞空泡化、萎缩、脱落和坏死。厄多司坦使肾小管损伤程度显著降低。结论是，氧化肾小管损伤在VCM诱导的肾毒性中起重要作用，用厄多司坦调节氧化应激可在生化和组织学水平上减轻VCM诱导的肾损伤。
