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 MT(1)/MT(2) antagonist), DH 97 (MT(2)), prazosin (MT(3)), 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 microM, 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 microM prevented lipid peroxidation, bringing the MDA levels to values of samples untreated by iron or LPS.
Requintina
Pura J
PJ
Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts, USA. requintina@cox.net
Oxenkrug
Gregory F
GF
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D000090023:Metallothionein 3; D051381:Rats; D011916:Rats, Inbred F344; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology*
D008070:Lipopolysaccharides; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D044094:Receptors, Melatonin; D017392:Thiobarbituric Acid Reactive Substances; D014363:Tryptamines; C057154:luzindole; D007501:Iron