Background: NADPH-cytochrome P450 reductase (CPR) is the electron donor protein for several oxygenase enzymes located in the endoplasmic reticulum. These oxygenases include P450 family enzymes involved in the metabolism of endogenous and exogenous substances. The enzyme is involved in adriamycin (anticancer drug) and paraquat (herbicide) toxicity. CPR is a flavoprotein containing both flavine-adenine dinucleotide and flavine mononucleotide. A structural study showed the presence of several sulfhydryl (SH) groups in the CPR molecule. Some of them play a key role in catalytic activity. As α-lipoic acid contains a disulfide bond, it may react with the SH group of CPR. The aim of the study was to evaluate the effect of α-lipoic acid on human P450 reductase activity. Methods: The activity of the enzyme was determined by measuring the rate of cytochrome c reduction at 550 nm, in vitro, using heart, liver and lung microsomes. Results: The activity of CPR was decreased in all organs after addition of α-lipoic acid to the reaction mixture at concentrations of 0.01, 0.10 and 1.00 mM. The decreases in CPR activity were concentration-dependent and the sequence of relative inhibition was as follows: heart >lung >liver. However, the statistical significance of CPR activity vs. control was observed in the heart in the presence of 1.00 mM α-lipoic acid and in the lung at 0.10 and 1.00 mM α-lipoic acid. Conclusion: α-Lipoic acid decreased NADPH-CPR activity in the lung and heart. The present results are promising for future studies to obtain the most effective antidote for adriamycin and paraquat toxicity.

Keywords:
NADPH-cytochrome P450 reductase, α-Lipoic acid, Human heart, Liver, Lung
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© 2006 S. Karger AG, Basel
2006
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