Protective effect of melatonin against alpha-naphthylisothiocyanate-induced liver injury in rats

The protective effect of melatonin against alpha-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis was examined in rats injected once with the toxicant (75 mg/kg body weight (BW)). In rats injected with ANIT alone, liver injury with cholestasis did not occur 12 hr after the injection but appeared at 24 hr, judging from the serum levels of marker enzymes and components. When melatonin (10 or 100 mg/kg BW) was orally administered to the ANIT-injected rats at 12 hr after the injection, the administered indoleamine dose-dependently prevented the formation of liver injury with cholestasis. In rats injected with ANIT alone, serum lipid peroxide (LPO) concentration increased 24 hr after the injection, while liver LPO concentration increased 12 hr after the injection and further increased at 24 hr. Myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, in the liver of the ANIT-injected rats increased 12 hr after the injection and further increased at 24 hr. The oral administration of melatonin (10 or 100 mg/kg BW) to the ANIT-injected rats attenuated the increases in serum and liver LPO concentrations and liver MPO activity found at 24 hr after the injection in a dose-dependent manner. These results indicate that orally administered melatonin at pharmacological doses protects against ANIT-induced liver injury with cholestasis in rats, and suggest that this protective effect of melatonin could be due to its antioxidant action and its inhibitory action against neutrophil infiltration in the liver of ANIT-injected rats.