[Effects of metallothionein on rifampicin (RFP)-induced hepatotoxicity in mice].
OBJECTIVE
To investigate the effect of metallothionein (MT) on rifampicin (RFP)-induced hepatotoxicity and the possible mechanisms.


METHODS
Male MT- I / II null (MT-/-) and wild type (MT+/+) mice were randomly divided into 4 groups, respectively, and were orally administered RFP (50, 100 or 200 mg/kg) or equal volumes of solvent daily for 15 consecutive days. Levels of plasma alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DB) were determined. Liver indexes were calculated and liver histopathologic changes were examined by hematoxylin and eosin (HE) staining. The content of glutathione (GSH) as well as the activities of glutathione peroxydase (GPx) and glutathione reductases (GR) were measured in the liver homogenates.


RESULTS
RFP treatment induced significant increases in plasma ALT, AST and DB, as well as liver index. Significant histopathologic changes which were charactered as fatty degeneration in liver were noteced. Moreover, augmentations of GSH content and GR activity and attenuation of GPx activity were observed. More severe hepatic injuries in MT-/- mice were observed as compared to MT+/+ mice, which were evidenced by higher liver/body weight ratio and GR activity, lower GSH content and GPx activity, and more serious fatty degeneration.


CONCLUSIONS
RFP-induced hepatotoxicity was associated with cholestasis and oxidative damage. MT -/- mice were more susceptible than MT +/+ mice to RFP-induced hepatotoxicity and the enhanced hepatotoxicity involves increased oxidative stress.
Lian
Yong
Y
Department of Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China.
Xu
Pei-Yu
PY
Ouyang
Zhao-He
ZH
Zhao
Jun
J
Wang
Yi-Mei
YM
Peng
Shuang-Qing
SQ
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D055786:Gene Knockout Techniques; D008099:Liver / Q000187:drug effects; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D012293:Rifampin / Q000037:antagonists & inhibitors / Q000633:toxicity*
D008668:Metallothionein; D012293:Rifampin