Boldine prevents human liver microsomal lipid peroxidation and inactivation of cytochrome P4502E1

Boldine, an alkaloid found in the leaves and bark of boldo, prevented the ferric-ATP catalyzed peroxidation of human liver microsomes. Lipid peroxidation, dependent upon electron transfer from NADPH or NADH, was comparably inhibited by boldine, with a K(I) value of about 5 microM. Inactivation and decreased content of human cytochrome P4502E1 as a consequence of incubating microsomes with ferric-ATP and reductant was completely prevented by boldine. However, inactivation of cytochrome P4502E1 by CCl4 was not prevented by boldine, although the alkaloid prevented CCl4-catalyzed lipid peroxidation. This suggests that the CCl4 inactivation of P4502E1 may be independent of CCl4-mediated lipid peroxidation. In view of its low toxicity, lack of effect on P450 activity, and strong inhibition of peroxidation of human liver microsomes, boldine may be valuable as an antioxidant and hepatoprotective agent.