The destruction of pulmonary and hepatic cytochrome P-450 by phthalaldehyde

Abstract

Addition of phthalaldehyde to pulmonary and hepatic microsomes resulted in destruction of cytochrome P-450 at all concentrations of phthalaldehyde tested. Phthalaldehyde destruction of pulmonary and hepatic cytochrome P-450 did not require NADPH. Addition of phthalaldehyde to pulmonary and hepatic microsomal suspension also resulted in inhibition of p-xylene hydroxylase and benzphetamine N-demethylase activities. The in vitro inhibition of p-xylene hydroxylase and benzphetamine N-demethylase as well as the destruction of P-450 could be prevented by supplementing microsomes with hepatic cytosol or purified aldehyde dehydrogenase. Lipid peroxidation did not occur when phthalaldehyde was added to either pulmonary or hepatic microsomes. It is suggested that phthalaldehyde can be used to study the in vitro drug metabolism reactions in these tissue preparations.