In vitro effects of calcium channel blockers and beta-adrenergic blocking agents on microsomal lipid perocidation and cytochrome p-450 content.

The effects of the calcium channel blockers (CCB) nifedipine (N), verapamil (V) and diltiazem (D) and the beta adrenergic blocking agents (BAB) propranolol (P) and atenolol (A) administered alone or in combination on lipid peroxidation (LPO) and cytochrome p-450 content were studied in rat liver microsomes. The drugs were tested in concentrations of 1 mM. V, A and P alone significantly decreased TBARS formed after in vitro stimulation of LPO by Fe2+ and ascorbate, whereas no antioxidant effect was found for N and D. A correlation between the antioxidant capacity of the drugs and their ability to protect cytochrome p-450 after in vitro stimulation of LPO was observed except for propranolol. Moreover, propranolol abolished cytochrome p-450 protecting effect of verapamil when administered together. A direct, LPO-independent decreasing effect on cytochrome p-450 was observed upon in vitro incubation of microsomes with propranolol. The results are discussed in terms of LPO-dependent degradation of cytochrome p-450, formation of propranolol reactive metabolites and propranolol-dependent changes in cytochrome lipid environment.