engleski

Dose- and time-dependent effects of luteolin in carbon tetrachloride-induced hepatotoxicity in mice

This study investigated the protective effects of luteolin on the carbon tetrachloride-induced hepatotoxicity in Balb/C mice. Luteolin was administered intraperitoneally (i.p.) at 5 or 50 mg/kg as a single dose or once daily for 2 consecutive days, respectively. Two hours after the last injection, the mice were treated with carbon tetrachloride (CCl4), 20 mg/kg, i.p. CCl4 treatment remarkably elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the serum. CCl4 induced oxidative stress in the liver, as indicated by decreased Cu/Zn superoxide dismutase (Cu/Zn SOD) activity and increased malondialdehyde (MDA) formation, and increased hepatic myeloperoxidase (MPO) activity, an indicator of neutrophil infiltration. Furthemore, CCl4 injection reduced the hepatic level of several trace elements and minerals and induced the expression of metallothionein (MT) in periportal hepatocytes. Treatment with luteolin prior to the administration of CCl4 significantly reduced AST and ALT activities in the serum and ameliorated oxidative stress. Luteolin administration also significantly reduced the myeloperoxidase activity, in a time- and dose-dependent manner. Pretreatment with 50 mg/kg of luteolin for 2 days remarkably elevated metal content to control values (Mg and Cu) and even above them (Zn and Fe). Furthermore, luteolin increased pericentral MT immunopositivity and shown histological architecture improvement being the most prominent in mice pretreated with 50 mg/kg of luteolin for 2 days. Luteolin pretreatment has shown the ability to reduce both the inflammatory process and oxidative stress. In conclusion, these results suggest the protective effect of luteolin on CCl4-induced hepatotoxicity and enhancement of hepatocyte proliferative capabilities.

carbon tetrachloride; luteolin; hepatotoxicity; metallothioneins; superoxide dismutase; myeloperoxidase; malondialdehyde

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