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

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

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.

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.

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.