Structure-activity Relationship in the Toxicity of Some Naturally Occurring Coumarins-chalepin, Imperatorin and Oxypeucedanine

Imperatorin, oxypeucedanine and chalepin are furanocoumarins isolated from Clausena anisata a medicinal plant common in West Africa. Only chalepin is found to have anticoagulant activity when administered to rats at a single dose. Aniline hydroxylase activity was appreciably depressed by each of the substances. Ethylmorphine demethylase, hepatic DNA, reduced glutathione and glucose-6-phosphatase were unaffected by these compounds when administered at a dose of 50 mg/kg for 3 days prior to sacrifice. Under similar conditions only chalepin treatment resulted in alpha-1-globulin increase and a decrease in beta-globulin content of the serum. Intraperitoneal treatment with chalepin (100 mg/kg) for 2 days resulted in the death of 4 rats out of 10 within a 48 h of treatment. Livers of dead rats showed generalized necrosis of hepatocytes. No deaths were recorded for imperatorin and oxypeucedanine. Rats surviving after 8 weeks showed no changes in hepatic enzyme activity, reduced glutathione and DNA concentrations. However, chalepin and imperatorin induced alterations in the serum protein pattern within this period. Liver lesions were observed in chalepin treated animals and were characterized by very mild necrosis of hepatocytes. No lesions were observed in the livers of rats treated with imperatorin and oxypeucedanine.