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

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 (MT2), prazosin (MT3), and 4‐P‐PDOT (MT2). 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 μM, 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.