Hyperbaric oxygen protects against lipopolysaccharide-stimulated oxidative stress and mortality in rats

Free radicals and proinflammatory mediators have been implicated in the pathogenesis of endotoxic shock, a disease with high mortality caused by Gram-negative bacterial endotoxin. Hyperbaric oxygen is used as an adjuvant therapy for various inflammatory diseases and shows beneficial effects in lipopolysaccharide-induced shock syndrome. However, the underlying mechanisms for these effects are still to be defined. In this study, we investigated the effect of hyperbaric oxygen on inflammatory mediators, free radicals, and mortality in endotoxic rats. Wistar-Kyoto rats were injected with lipopolysaccharide (10 mg/kg) and then exposed to aminoguanidine, an inhibitor of inducible nitric oxide (NO) synthase (bolus injection 2 h after lipopolysaccharide), or hyperbaric oxygen (2 ATA for 60 min 1, 4, 9, and 24 h after lipopolysaccharide). Plasma tumor necrosis factor alpha (TNF-α), NO, and superoxide anion were detected and the vasorelaxation response and survival rate were assessed. The results demonstrated that increases in plasma TNF-α and NO, and the vasohyporeactivity induced by lipopolysaccharide treatment were significantly inhibited by hyperbaric oxygen and aminoguanidine. Mortality and vascular superoxide anion production of lipopolysaccharide treatment were also markedly reduced by hyperbaric oxygen treatment, but were not restored by aminoguanidine. None of the parameters was changed by hyperbaric oxygen treatment alone. Thus, repeated hyperbaric oxygen exposure significantly attenuated the inflammatory mediators, free radicals, and mortality in endotoxic rats.