Effect of Luzindole and Other Melatonin Receptor Antagonists on Iron- and Lipopolysaccharide-Induced Lipid Peroxidation in Vitro

摘要

Melatonin and its precursor, N-acetylserotonin (NAS), have been shown in in vivo and in vitro studies to inhibit iron- and lipopolysaccharide (LPS)-induced lipid peroxidation in rats and mice. Using in vitro studies, we examined whether these effects will be affected by the melatonin receptor antagonists luzindole (a competitive MT1 /MT2 antagonist), DH 97 (MT 2), prazosin (MT3 ), and 4-P-PDOT (MT 2). Lipid peroxidation in the form of malondialdehyde (MDA) was assayed by measuring thiobarbituric acid—reactive substances. The antagonists did not affect the melatonin and NAS effect on iron- and LPS-induced peroxidation. However, luzindole alone, but not the other antagonists, inhibited the iron- and LPS-induced peroxidation in the rat brain and kidney homogenates. At a dose of 50 μ M, luzindole reduced iron-induced MDA levels by 80% in the brain and 84% in the kidney, whereas LPS-induced MDA levels were reduced by 85% in both brain and kidney. A dose of 800 μM prevented lipid peroxidation, bringing the MDA levels to values of samples untreated by iron or LPS.