Hiromi Kotani

The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver damage during early phase of endotoxemia in rats

Lipopolysaccharide (LPS)-induced endotoxemia produces nitric oxide (NO); however, the role of the NO during endotoxemia is still controversial. The aim of this study was to investigate a role of LPS-induced NO during the early phase of endotoxemia. Wistar rats were intraperitoneally injected with saline or LPS at various doses (0.001, 0.01, or 5 mg/kg), and intra-abdominal NO concentration was determined by chemiluminescence before and after LPS administration at indicated times (1, 2, 6, 10, and 18 h). Serum aspartate aminotransferase and alanine aminotransferase levels were determined and histological examination was performed 10 h after LPS administration to assess liver damage. N(G)-nitro-L-arginine-methyl ester (L-NAME), a nonselective inhibitor of NO synthase, was used to investigate the possible roles of NO during LPS-induced endotoxemia. The intra-abdominal NO concentration was elevated within 2 h and reached a maximal level at 10 h after low doses of LPS injection (0.001 and 0.01 mg/kg) while liver damage was not observed. After high-dose LPS (5 mg/kg) administration, liver damage was observed and intra-abdominal NO was elevated continuously until 18 h. A time course study revealed very similar patterns of intra-abdominal NO increase after the three different dose of LPS at each times points during the first 10 h. Pretreatment of L-NAME inhibited the intra-abdominal NO release and aggravated the liver damage caused by low doses (0.001 and 0.01 mg/kg) of LPS as well as high dose (5 mg/kg) of LPS. Therefore, NO, released during the first 10 h after LPS injection, may play a cytoprotective role in the liver.

Protective Effect of Nitric Oxide on Acute Liver Failure in Rats

The effect of low-dose lipopolysaccharide (LPS)-induced nitric oxide (NO) on liver damage and survival in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. There was marked elevation of serum aspartate aminotransferase and alanine aminotransferase levels 24 h after D-gal. These aminotransferases were significantly improved in low-dose LPS-pretreated rats at 24 h after the administration of D-gal. Ninety percent of control animals died within 4 days after D-gal injection but pretreatment of low-dose LPS significantly decreased mortality to 10%. N G-Nitro-L-arginine-methyl ester, but not N G-nitro-D-arginine-methyl ester, reversed this cytoprotection. In conclusion, pretreatment of low-dose LPS prevents experimental liver failure through activation of endogenous NO synthesis.