Abstract

Nitric oxide (NO) from artificial NO donors induces cell death through complete inhibition of mitochondrial respiration of hepatocytes. Treatment of hepatocytes with lipopolysaccharide (LPS) and cytokine mixture (interferon γ and tumor necrosis factor α) not only results in NO production but also causes cellular respiration suppression and cell death in hepatocytes. NG-monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase, inhibits hepatocyte NO synthesis but cannot prevent hepatocytes from LPS and cytokine mixture-induced cellular injuries. Similarly, some metabolic intermediates capable of inhibiting hepatocyte NO synthesis cannot block LPS and cytokine mixture-mediated cellular injuries in hepatocytes. These results imply that lipopolysaccharide and cytokine mixture-induced cellular injuries and NO syntheses are parallel events, NO is not involved in LPS and cytokine mixture-induced cell damage.

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