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来曲唑诱导肝毒性而不引起氧化应激:褪黑素的保护作用。

Letrozole induces hepatotoxicity without causing oxidative stress: the protective effect of melatonin.

机构信息

Medical Faculty of Mustafa Kemal University, Department of Physiology, Hatay, Turkey.

出版信息

Gynecol Endocrinol. 2011 Apr;27(4):209-15. doi: 10.3109/09513590.2010.488769. Epub 2010 Jun 8.

DOI:10.3109/09513590.2010.488769
PMID:20528203
Abstract

AIM

The aim of this study was to determine the effects of letrozole (LTZ), an aromatase inhibitor (AI), and melatonin (MLT) on hepatic function and oxidative stress in female rats.

MATERIAL AND METHODS

A total of 32 female rats were divided equally into four groups (n = 8). Control group received saline (0.5 ml/day, oral gavage). LTZ was administered to rats by daily oral gavage at 1 mg/kg dose. LTZ + MLT group was given LTZ (1 mg/kg, oral gavage) plus MLT (0.5 mg/kg/day, s.c.). MLT group was given MLT (0.5 mg/kg/day) by s.c. injection. The activities of superoxide dismutase (SOD) and catalase (CAT) and malondialdehyde (MDA) levels were measured in liver tissue. Total antioxidant capacity (TAC), total oxidant status (TOS), ALT, AST, GGT, ALP, LDH, bilirubin, BUN, creatinine, total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG) were assayed in serum samples.

RESULTS

The oxidative stress parameters did not differ between groups. LTZ administration increased hepatic function parameters such as AST, LDH, ALP, bilirubin and MLT improved the disturbances of hepatic function. LTZ caused minimal histological changes in liver tissue and MLT treatment reversed those dejenerations.

DISCUSSION

LTZ may cause hepatotoxicity without inducing oxidative stress and MLT restores hepatic activity.

摘要

目的

本研究旨在确定芳香酶抑制剂(AI)来曲唑(LTZ)和褪黑素(MLT)对雌性大鼠肝功能和氧化应激的影响。

材料与方法

将 32 只雌性大鼠等分为 4 组(n = 8)。对照组给予生理盐水(0.5 ml/天,灌胃)。大鼠每日灌胃给予来曲唑 1mg/kg。LTZ+MLT 组给予来曲唑(1mg/kg,灌胃)加 MLT(0.5mg/kg/天,皮下注射)。MLT 组给予 MLT(0.5mg/kg/天)皮下注射。测量肝组织中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性以及丙二醛(MDA)水平。测定血清中总抗氧化能力(TAC)、总氧化状态(TOS)、ALT、AST、GGT、ALP、LDH、胆红素、BUN、肌酐、总胆固醇(TC)、高密度脂蛋白(HDL)和甘油三酯(TG)。

结果

各组间氧化应激参数无差异。来曲唑给药增加了 AST、LDH、ALP、胆红素等肝功能参数,MLT 改善了肝功能紊乱。来曲唑导致肝组织出现轻微的组织学变化,而 MLT 治疗逆转了这些退行性变化。

讨论

LTZ 可能导致肝毒性而不诱导氧化应激,而 MLT 恢复肝活性。

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