Species differences in the hepatotoxicity of coumarin: a comparison of rat and Mongolian gerbil

The acute hepatic effects of coumarin (2H-1-benzopyran-2-one) in male Wistar rats and Mongolian gerbils has been compared. A single dose of coumarin (125 mg/kg, intraperitoneally (i.p.)) was hepatotoxic to rats within 24 h as assessed by its effects on a variety of hepatic parameters. Coumarin-induced hepatotoxicity was associated with significant increases in relative liver weight, plasma alanine and aspartate aminotransferase activities and hepatic non-protein sulphydryl groups. Cytochrome P-450 content and 7-ethoxycoumarin O-deethylase and glucose 6-phosphatase activities were significantly lower in coumarin-treated compared with control rats. Centrilobular necrosis was only observed in two out of six rats at this dose, but was present in all four coumarin-treated rats when the dose was increased to 150 mg/kg. In contrast to the effects observed in the rat, no evidence was found for coumarin-induced hepatotoxicity in gerbils following a single i.p. dose of 125 mg/kg. These data indicate that the gerbil is less sensitive to the hepatotoxic effects of coumarin than the rat.