title: Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats.
abstract: Mitochondrial nitric oxide synthase (mtNOS) is expressed constitutively, although it might be induced. Nitric oxide (NO) is a physiological regulator of mitochondrial respiration. Melatonin prevents mitochondrial oxidative damage and inhibits iNOS expression induced by bacterial lipopolysaccharide (LPS). The loss of melatonin with age may be related to the age-dependent mitochondrial damage. Thus, we examined the protective role of melatonin against the effects of LPS on mtNOS and on respiratory complexes activity in liver and lung mitochondria from young and old rats. The activity of mtNOS in control lung was low and did not change with age. LPS administration (10 mg/kg, i.v.) significantly increased mtNOS expression and activity and NO production in lung mitochondria, and the effect was greater in old rats. LPS administration also reduced the age-dependent decrease of the respiratory complexes I and IV. Melatonin administration (60 mg/kg, i.p.) prevented the LPS toxicity, decreasing mitochondrial NOS activity and NO production. Melatonin also counteracted LPS-induced inhibition of complexes I and IV. In general, the actions of melatonin were stronger in older animals than in younger ones. The results suggest that an inducible component of mtNOS, together with mitochondrial damage, occurs during sepsis, and melatonin prevents the mitochondrial failure that occurs during endotoxemia.
authors.affiliation: Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Josefa
authors.initials: J
authors.lastname: León
authors.forename: Manuel
authors.initials: M
authors.lastname: Macías
authors.forename: Huda
authors.initials: H
authors.lastname: Khaldy
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009573:Nitrites; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D008550:Melatonin