Endogenous hydrogen sulfide formation mediates the liver damage in endotoxemic rats.

BACKGROUND: Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter and may play important roles in normal physiology and liver disease. AIMS: To investigate the relationships between the formation of liver H2S and liver damage in endotoxemic rats caused by lipopolysaccharide (LPS).
METHODS: Male SD rats were sacrificed to acute endotoxemia and pretreated with H2S donor sodium hydrogen sulfide (NaHS) or H2S inhibitor dl-propargylglycine (PAG). Liver H2S concentration, liver cystathionine-γ-lyase (CSE) mRNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level, liver histopathological alteration in different time after treatment were determined.
RESULTS: Endotoxemia resulted in an increase in serum levels of ALT and AST. In the liver, endotoxemia induced a significant increase in the H2S concentration, and in the expression of the H2S-synthesizing enzymes CSE. Pretreatment with NaHS promoted the increase the liver H2S concentration and aggravated the LPS-induced liver damage, However, administration of PAG abolished the increase the liver H2S concentration and reduced the liver injury caused by endotoxemia.
CONCLUSIONS: These findings support the view that an enhanced formation of H2S contributes to the liver injury in endotoxemia. We propose that inhibition of H2S synthesis may be a useful therapeutic strategy against the liver injury associated with endotoxemia.