Alov P, Koleva M, Kastelova A
Department of Drug Toxicology, Institute of Physiology, Bularian Academy of Sciences, Sofia.
Exp Toxicol Pathol. 1999 Jul;51(4-5):277-81. doi: 10.1016/s0940-2993(99)80005-0.
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.
研究了钙通道阻滞剂（CCB）硝苯地平（N）、维拉帕米（V）和地尔硫䓬（D）以及β肾上腺素能阻滞剂（BAB）普萘洛尔（P）和阿替洛尔（A）单独或联合给药对大鼠肝微粒体脂质过氧化（LPO）和细胞色素p - 450含量的影响。药物以1 mM的浓度进行测试。单独使用V、A和P可显著降低Fe2 +和抗坏血酸体外刺激LPO后形成的硫代巴比妥酸反应物（TBARS），而未发现N和D具有抗氧化作用。除普萘洛尔外，观察到药物的抗氧化能力与其在体外刺激LPO后保护细胞色素p - 450的能力之间存在相关性。此外，普萘洛尔与维拉帕米一起给药时会消除维拉帕米对细胞色素p - 450的保护作用。在微粒体与普萘洛尔进行体外孵育时，观察到对细胞色素p - 450有直接的、不依赖LPO的降低作用。根据细胞色素p - 450的LPO依赖性降解、普萘洛尔活性代谢物的形成以及普萘洛尔依赖性细胞色素脂质环境变化对结果进行了讨论。
