Antiperoxidative effects of platelet activating factor antagonists against iron-dependent lipid peroxidation in murine ventricular membranes.
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abstract
Platelet activating factor (PAF) antagonists have been recently documented to possess beneficial effects on ischemia and ischemia-reperfusion-induced myocardial injury. Moreover, their ameliorative effect has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study, the effect of PAF antagonists BN 52021, BN 52030 and BN 52039 on iron-initiated lipid peroxidation (LPO) was investigated in murine ventricular membranes and compared with a potent antioxidant, U-74500A ( a lazaroid). Fe2+ -Vitamin C induced a concentration and time-dependent LPO, measured as thiobarbituric acid reactive substances (TBARS) by standard malondialdehyde (MDA) curve. PAF antagonists were pretreated to ventricular membranes in 5 microM and higher concentrations. All three agents inhibited Fe2+ -Vitamin C-initiated LPO in a concentration-dependent manner with an IC50 value ranging from 103.7 to 373.5 microM; however, they were less potent than U-74500A (IC50 6.8 microM). Inhibition of LPO may not be due to their classical pharmacological actions, but may be attributed to characteristic chemical structure or their physicochemical interactions with biological membranes. Inhibition of LPO may provide additional cardioprotective activity and thus reaffirms their use in ischemic heart disease.
