Inhibition of H2S Production Reduces Portal Pressure and Attenuates Liver Fibrosis in Bile Duct-Ligated Rats.

INTRODUCTION

Hydrogen sulfide (H2S) is a gaseous signalling molecule with vasodilatory properties and regulates inflammation and fibrosis in the liver.

METHODS

Rats with bile duct ligation (BDL)-induced liver disease were treated with propargylglycine (PAG; 30 mg/kg via intragastric gavage), a selective inhibitor of cystathionine γ-lyase, the main source of H2S in the cardiovascular system and liver, or vehicle. PAG treatment was initiated at day 5 after BDL to evaluate its effects on the progression of liver fibrosis and portal hypertension.

RESULTS

In BDL rats, PAG significantly reduced portal pressure (PP) (10.4 ± 2.7 mm Hg versus 16.0 ± 3.9 mm Hg, p < 0.05) without affecting systemic pressure. In mesenteric arteries mounted on a wire myograph, no differences were observed in responses to acetylcholine and H2S donor sodium hydrosulfide between treated and untreated BDL rats. In the liver, PAG treatment significantly reduced the expression of IL-6, TGF-β, and collagen I and markedly attenuated hepatic fibrosis and architectural distortion. Rats treated with PAG also exhibited significantly lower alanine aminotransferase.

CONCLUSION

In BDL rats, inhibition of H2S synthesis decreases PP and attenuates liver fibrosis, suggesting that targeting H2S may represent a therapeutic strategy for portal hypertension, potentially through modulation of intrahepatic resistance.