Effect of dimethyl-4,4 '-dimethoxy-5,6,5 ',6 '-dimethylenedioxybiphenyl-2,2 '-dicarboxylate (DDB) on chemical-induced liver injury

The effects of orally administered dimethyl-4,4'-dimethoxy-5,6,5',6'-dimeth ylene-dioxybiphenyl-2,2'-dicarboxylate (DDB) on the hepatotoxicity induced by carbon tetrachloride, acetaminophen or ethanol were investigated in rats and mice. Either single or repeated DDB pretreatment (50 or 200 mg/kg) did not alter the hepatotoxicity induced by carbon tetrachloride (0.2 or 1.0 m l/kg, i.p.) in female rats as indicated by increases in the activity of ala nine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) in serum. The hepatotoxicity of acetaminophen (350 mg/k g, i.p.) was also unaffected in male mice pretreated with DDB (50 mg/kg/d) for a week. However, DDB administration (50 mg/kg/d for 7 d) decreased the hepatic fatty degeneration induced by repeated ethanol treatment (0.75 g/kg , i.p., x2 times a day for a week) in rats as shown by the accumulation of triglycerides and cholesterol in the liver. Malondialdehyde (MDA) formation in liver homogenates was inhibited by DDB treatment. The significance of t he action of DDB on alcoholic fatty liver generation in clinical settings i s discussed.