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Several naturally occurring furanocoumarins significantly inhibited microsomal lipid peroxidation not only mediated by endogeneous iron and NADPH but also initiated by CCl4, metabolites. Phellopterin, a potent inhibitor of cytochrome P-450, exhibited an almost complete inhibition of CCl4-induced hepatotoxicity as measured by sGPT activity 24 hr after CCl4 intoxication, whereas other furanocoumarins such as imperatorin, byakangelicin and oxypeucedanin methanolate exerted no protective effect. When compared with other cytochrome P-450 inhibitors (SKF-525A, AIA) and silymarin given at the same dose level (ED50), phellopterin still showed a significant inhibition of hepatotoxicity which was even stronger than that of AIA, known as a typical suicide inhibitor. Phellopterin was partially effective when given 30 min after CCl4 treatment. Repeated administrations of phellopterin, however, resulted in a complete loss of the protection against CCl4-induced hepatotoxicity.
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