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

被引:18
作者
Aydin, Mehmet [2 ]
Oktar, Suleyman [1 ]
Ozkan, Orhan Veli [3 ]
Alcin, Ergul [4 ]
Ozturk, Oktay Hasan [5 ]
Nacar, Ahmet [6 ]
机构
[1] Mustafa Kemal Univ, Fac Med, Dept Pharmacol, TR-31040 Antakya, Turkey
[2] Mustafa Kemal Univ, Fac Med, Dept Physiol, TR-31040 Antakya, Turkey
[3] Mustafa Kemal Univ, Fac Med, Dept Gen Surg, TR-31040 Antakya, Turkey
[4] Firat Univ, Fac Med, Dept Physiol, TR-23169 Elazig, Turkey
[5] Mustafa Kemal Univ, Fac Med, Dept Biochem, TR-31040 Antakya, Turkey
[6] Mustafa Kemal Univ, Fac Med, Dept Histol, TR-31040 Antakya, Turkey
关键词
Letrozole; melatonin; hepatotoxicity; oxidative stress; estrogens; POSTMENOPAUSAL WOMEN; BREAST-CANCER; ANTIOXIDANT; ESTRADIOL; TAMOXIFEN; INJURY; EXPRESSION; RELEVANCE; ISCHEMIA; RECEPTOR;
D O I
10.3109/09513590.2010.488769
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:209 / 215
页数:7
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