Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver

Increasing evidence regarding free radical-generating agents and inflammato ry processes suggests that accumulation of reactive oxygen species can caus e hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydr operoxide (t-BHP), can be metabolized to free radical intermediates by cyto chrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t- BHP Co induce hepatotoxicity in vitro and in vivo and determined the antiox idative bioactivity of esculetin, a coumarin compound. Our investigations s howed that pretreatment with esculetin (5-20 mug/ml) significantly decrease d the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT) , and also decreased the formation of malondialdehyde (MDA) in primary cult ured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo s tudy in rats showed that pretreatment with esculetin (i.p.) at concentratio ns of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mm ol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyt e infiltration, and necrosis. Based on the results described above, we spec ulate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems.