Protective Effect Of Sodium Acetate Against Endotoxic Shock And Its Anti-inflammatory Mechanism

Sepsis is a common clinical illness, more than 50 % mortality rate. We searched both from in vivo and in vitro experiments, to study protective effect of sodium acetate against endotoxic shock sodium acetate by LPS and its anti-inflammatory mechanism, in order to provide a theoretical basis for better understanding acetate which is the most important short-chain fatty acids of the beneficial effect for human, and to provide experimental evidence for development of acetic acid and acetic acid salt health food drinks.In vivo by administering different dose of NaAc respectively, after 30 min were injected D-GalN/LPS to induce acute hepatic failure. The mortality and liver injury were observed, and the serum ALT, the tumor necrosis factorαand nitrite oxide (NO) were detected. In vitro the RAW264.7 macrophage cells were pretreated 30 min with different doses of NaAc, then LPS-induced the production of inflammatory cytokines. The effects of different doses of NaAc on proliferation of RAW264.7 macrophages were measured by MTT assay and the optimal dose was chosen. The production of NO was detected. The secretion of iNOS in the supernatant was determined by ELISA. The effects of NaAc on nuclear factor-κB (NF-κB) activation in RAW264.7 macrophages with LPS induction were measured by immunocytochemical method and Western Blotting respectively.The results suggested that NaAc pre-administration reduced liver injury and the mortality, diminished the production of ALT and NO, and the protective effect was inhibition of pro-inflammatory cytokines such as TNF-αand NO production. One of the mechanisms was that NaAc inhibits the activation of NF-κB in RAW264.7 macrophages inducedby LPS, and inhibited the translocation of NF-κB/p65 from cytoplasm to nuclear, which may be the possible mechanism responsible for the inhibition of NaAc on the expression of iNOS and the production of TNF-αand NO.