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


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.


CONCLUSIONS
LTZ may cause hepatotoxicity without inducing oxidative stress and MLT restores hepatic activity.
Medical Faculty of Mustafa Kemal University, Department of Physiology, Hatay, Turkey.
Mehmet
M
Aydin
Süleyman
S
Oktar
Orhan Veli
OV
Ozkan
Ergül
E
Alçin
Oktay Hasan
OH
Oztürk
Ahmet
A
Nacar
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D000077289:Letrozole; D008099:Liver / Q000187:drug effects*; D008550:Melatonin / Q000627:therapeutic use; D009570:Nitriles / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000009:adverse effects*
D000975:Antioxidants; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D008550:Melatonin