Differential Effects of Lipopolysaccharide on Lipid Peroxidation in F344N, SHR Rats and BALB/c Mice, and Protection of Melatonin and NAS against Its Toxicity

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.