Comparative antioxidant effects of beta-adrenoceptor blockers, calcium antagonists and U-74500A against iron-dependent lipid peroxidation in murine ventricular microsomal membranes

Methods Find Exp Clin Pharmacol. 1996 Nov;18(9):559-67.

Abstract

Recently we have shown that ACE inhibitors and platelet activating factor antagonists inhibit iron-dependent lipid peroxidation in murine ventricular membranes and possess beneficial effects on ischemia and ischemia reperfusion-induced myocardial injury, which has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study we investigated the effects of beta-adrenoceptor blockers and calcium antagonists on iron-dependent lipid peroxidation (LPO) in murine ventricular membranes and compared them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced LPO in a concentration- and time-dependent manner, measured as thiobarbituric acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5 microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration-dependent manner with IC50 values of 192.8-208.3 microM; however, they were less potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem and nifedipine inhibited LPO at very high concentrations with IC50 values of 864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical pharmacological actions, but rather to their characteristic chemical structures or physicochemical interactions with biological membranes. In view of the pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by gallopamil, verapamil, propranolol and metaprolol may provide additional cardioprotective activity and thus reinforces their beneficial effects in the treatment of ischemic heart disease.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Antioxidants / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Culture Techniques
  • Female
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Iron / metabolism
  • Lipid Peroxidation / drug effects*
  • Male
  • Mice
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Pregnatrienes / pharmacology*
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Adrenergic beta-Antagonists
  • Antioxidants
  • Calcium Channel Blockers
  • Pregnatrienes
  • Thiobarbituric Acid Reactive Substances
  • Iron
  • U 74500A