Comparative effects of antioxidants on the toxicity of mixed pyrrolizidine alkaloids from Senecio jacobaea in mice.

The comparative effects of the antioxidants, butylated hydroxyanisole (BHA), ethoxyquin, and cysteine on pyrrolizidine-alkaloid-induced (PA-induced) lethality and acute hepatotoxicity were assessed in female mice. Diets containing 0.75% BHA, 0.25% ethoxyquin, or 1% cysteine were fed to mice for 10 d before the ip administration of mixed PAs from Senecio jacobaea (tansy ragwort), 280 mg/kg. Without the dietary antioxidants, the PAs produced 100% mortality in 24 h. The BHA and ethoxyquin diets were completely and partially protective, respectively, against the PA-induced lethality. The deaths were associated with severe hemorrhagic lesions in liver with or without hepatocytic necrosis. Both BHA and ethoxyquin significantly reduced the incidence of the hemorrhagic lesions but not the necrotic lesions in liver. Cysteine had no significant effect on either mortality or the liver lesions induced by the mixed PAs. These results suggest that dietary antioxidants have differential protective effects against lethality and acute hepatotoxicity induced by mixed PAs from tansy ragwort.