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阿霉素诱导的高脂血症性肾病:褪黑素给药的作用

Hyperlipidemic nephropathy induced by adriamycin: effect of melatonin administration.

作者信息

Montilla P, Túnez I, Muñoz M C, López A, Soria J V

机构信息

Department of Biochemistry and Molecular Biology, University of Córdoba School of Medicine, Spain.

出版信息

Nephron. 1997;76(3):345-50. doi: 10.1159/000190202.

DOI:10.1159/000190202
PMID:9226237
Abstract

The effect of melatonin (MEL) on the nephropathy and the oxidative stress induced by a single and high dose of Adriamycin (AD) has been studied in Wistar male rats. MEL (50 microg/kg/day) was injected intraperitoneally 3 and 7 days, respectively, before and after AD injection (20 mg/kg i.p.). Trunk blood was drawn and triglycerides, total cholesterol, phospholipids, high-density lipoprotein cholesterol, urea, creatinine, total protein, lipoperoxides, and reduced glutathione (GSH) levels and catalase activity (CAT) were determined in serum. In kidney homogenates, lipoperoxides, GSH, and CAT were measured as well as total protein in urine. AD administration resulted in hyperlipidemia and high-grade proteinuria and a marked increase in serum lipoperoxides, urea, and creatinine. In the kidney, the increase in lipoperoxides was accompanied by a significant decrease of GSH and CAT. The efficiency of MEL was specially remarkable in restoring GSH, CAT, and proteinuria to the levels of controls. These results confirm the involvement of free radicals in the pathogenesis of nephrotoxicity induced by AD. Likewise, they show the high antioxidative power of MEL and its marked effect on the prevention and suppression of this nephropathy.

摘要

在雄性Wistar大鼠中研究了褪黑素(MEL)对单次大剂量阿霉素(AD)诱导的肾病和氧化应激的影响。在腹腔注射AD(20mg/kg)之前3天和之后7天,分别腹腔注射MEL(50μg/kg/天)。采集大鼠的股静脉血,测定血清中的甘油三酯、总胆固醇、磷脂、高密度脂蛋白胆固醇、尿素、肌酐、总蛋白、脂过氧化物、还原型谷胱甘肽(GSH)水平及过氧化氢酶活性(CAT)。检测肾匀浆中的脂过氧化物、GSH、CAT以及尿中的总蛋白。给予AD导致高脂血症和重度蛋白尿,血清脂过氧化物、尿素和肌酐显著升高。在肾脏中,脂过氧化物增加伴随着GSH和CAT的显著降低。MEL在将GSH、CAT和蛋白尿恢复至对照水平方面的效果尤为显著。这些结果证实了自由基参与了AD诱导的肾毒性的发病机制。同样,它们表明MEL具有高抗氧化能力及其对预防和抑制这种肾病的显著作用。

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