title: Differential effects of lipopolysaccharide on lipid peroxidation in F344N, SHR rats and BALB/c mice, and protection of melatonin and NAS against its toxicity.
abstract: The effect of bacterial lipopolysaccharide (LPS) injection on the lipid peroxidation process in Fischer (F344N) rats, spontaneously hypertensive (SHR) rats, and BALB/c mice was studied. Lipid peroxidation, as measured by malondialdehyde + 4-hydroxyalkenals (MDA + HAE) levels, was decreased in brain, kidney, and liver homogenates of F344N rats injected with lower LPS doses of 0.5, 1.0, and 2.0 mg/kg, but was increased with the highest dose of 10 mg/kg body weight. The dose of 10 mg/kg LPS decreased the MDA + HAE levels in SHR brain homogenates and increased levels in the liver homogenates. MDA + HAE levels in the brain and liver but not kidney homogenates in BALB/c mice also increased after administration of LPS at the highest dose (10 mg/kg body weight). The effect of melatonin, N-acetylserotonin (NAS), and GR-135,531 (a melatonin ligand with high affinity for MT3 receptor) on the survival of BALB/c mice injected with lethal dose of LPS was also tested. A single dose of 5 mg/kg of melatonin or NAS simultaneously injected with LPS (25 mg/kg body weight) markedly protected mice from the lethal effect of LPS with survival rates of 90% and 95% for melatonin and NAS, respectively, and 59% for mice injected with just LPS after 24 hours; a survival rate of 50% for both melatonin and NAS, and 32% was obtained for mice injected with just LPS after five days. GR-135,531 did not show protection against a lethal dose of LPS. Our results indicated that the effect of LPS on lipid peroxidation is dose-, time-, and species-dependent, and that melatonin and NAS are equally effective in protecting mice from lethality caused by LPS.
authors.affiliation: Pineal Research Laboratory, Department of Psychiatry, St. Elizabeth's Medical Center, Boston, Massachusetts, USA. requintina@cox.net
authors.forename: Pura J
authors.initials: PJ
authors.lastname: Requintina
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Oxenkrug
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism*; D014020:Tissue Extracts / Q000378:metabolism
chemical_list: D000475:Alkenes; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D014020:Tissue Extracts; D012701:Serotonin; D008315:Malondialdehyde; D008550:Melatonin; C006389:N-acetylserotonin