Age-dependent lipopolysaccharide-induced iNOS expression and multiorgan failure in rats: effects of melatonin treatment.
Senescence amplifies the sensitivity to endotoxemia, which correlates with increased nitric oxide (NO) levels and mortality. Melatonin displays antioxidant and anti-inflammatory effects, but its levels decrease with age. Lipopolysaccharide (LPS) (10 mg/kg) was injected to 3- and 18-month-old rats 6 h before they were killed, and melatonin (60 mg/kg) was injected before and/or after LPS. Inducible nitric oxide synthase (iNOS) expression and activity, nitrite content, lipoperoxidation (LPO) levels, and serum markers of liver, renal, and metabolic dysfunction, were measured in liver and lung of these animals. An age-dependent increase in iNOS activity, NO content, and LPO levels was observed, and these changes were augmented further by LPS. Melatonin decreased the expression and activity of iNOS, reducing NO and LPO levels to basal values in both septic LPS-treated groups. Liver, kidney, and metabolic dysfunctions were also significantly higher in aged that in young rats and further increased by LPS. Melatonin treatment counteracted these alterations in young and aged septic rats. Melatonin reduced LPS-dependent iNOS expression and multiorgan failure in a similar extent in young and aged rats. Because aged rats showed higher organ and metabolic impairment than young animals in response to LPS, the results also suggest an increased efficacy of the anti-septic properties of melatonin in the aged animals.
Escames
Germaine
G
Instituto de Biotecnología, Departamento de Fisiología, Universidad de Granada, Avda. de Madrid 11, E-18012 Granada, Spain.
López
Luis C
LC
Ortiz
Francisco
F
Ros
Eduardo
E
Acuña-Castroviejo
Darío
D
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D019446:Endotoxemia / Q000188:drug therapy; D004790:Enzyme Induction / Q000502:physiology; D007267:Injections; D007674:Kidney Diseases / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000032:analysis; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008659:Metabolic Diseases / Q000188:drug therapy; D009102:Multiple Organ Failure / Q000188:drug therapy*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D008070:Lipopolysaccharides; D009573:Nitrites; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008550:Melatonin