INHIBITION OF ENDOGENOUS HYDROGEN SULPHIDE FORMATION PROTECTS THE LIVER FROM HEPATIC ISCHEMIA-REPERFUSION INJURY IN THE RAT

Abstract

Hydrogen sulphide (H2S) is a naturally occurring gas with important roles both in physiology and disease. Cystathionine-γ-lyase (CSE) and cystathionine-β-synthase utilize L-cysteine as substrate to form H2S. The role of H2S in inflammation is beginning to emerge. Recent evidence has suggested that endogeous H2S plays a role in the pathophysiology of cerulean-induced pancreatitis, hemorrhagic shock, endotoxemia, and in local inflammation. Hence, the present study was designed to investigate the role of endogenous H2S in ischemia-reperfusion (I/R) injury of the liver. Male Wistar rats were pre-treated with DL-propargylglycine (PAG) (100 mg/kg, i.p.): (i) 30 min before the blood supply to 3/4 of the liver was interrupted for 45min and followed by 2h of reperfusion (n = 9), or (ii) 5 min prior to onset of reperfusion (n = 6). Blood samples were obtained at the end of reperfusion for determination of biochemical markers of liver injury, kidney or pancreatic dysfunction, and oxidative stress (MDA). Tissue samples were also collected for histology. Treatment with PAG 30 min prior to ischemia significantly reduced the increase in ALT (229 ± 24 vs. 1603 ± 318 IU/L), and γ-GT (0.2 ± 0.04 vs. 0.6 ± 0.03 IU/L) serum levels as well as the increase in MDA levels (1.9 ± 0.3 vs. 3.2 ± 0.4 μM) caused by I/R injury. The same results were obtained when treatment with PAG was performed before the onset of reperfusion. In contrast, the increase in AST or LDH caused by I/R of the liver were not significantly reduced by PAG. In conclusion, these findings support the view that endogenous H2S contributes to the tissue injury caused by I/R of the liver, and that inhibition of H2S synthesis may represent a new therapeutic strategy for the management of liver I/R injury.