The impact of hydrogen sulfide on mesenchymal stem cells in rats suffering from liver fibrosis via suppression of TGF-β signaling

Abstract

Worldwide, liver fibrosis (LF) causes complications and has an elevated death rate. The prevalence of mesenchymal stem cell therapy (MSC) is a result of the lack of liver donors. In recent years, the study of stem cell therapy has advanced into a promising and cutting-edge field of study. The purpose of this study is to assess the possible value of in vitro preconditioning of bone marrow-derived mesenchymal stem cells (BMSCs) with sodium hydrogen sulfide (NaHS), which aims to encourage rats to benefit from stem cell therapy with carbon tetrachloride-induced liver fibrosis. Materials and Methods: Fifty male albino rats (6 weeks old & 120–150 g) were divided equally into 5 groups (10 rats each); the 1st group served as a negative control, the 2nd group was a positive control, in which rats received 2 mL/kg CCl4 (1:1 corn oil) twice a week for five weeks, and the remaining three groups received, in addition to CCL4, a NaHS solution (10 μmol/kg) every 2 days for 6 weeks, one dose of BMSCs (3 × 10⁶ cells per rat) intravenously, and a single dose of BMSCs (3 × 10⁶ cells per rat) in culture with 200 μmol/L NaHS for 24 h. Quantitative gene expression of transforming growth factor-beta (TGF-β), Smad, collagen, α-SMA, MAPK, β-catenin, GSK-3B, and CBS was carried out using real-time polymerase chain reaction; whereas the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were estimated using colorimetric analysis. Also, the relative expression of MAPK, β-catenin, and GSK-3B by Western blot was done. Histopathological analysis was used to gauge the progression of LF. Results: The liver fibrosis group exhibited significantly increased serum ALT and AST levels, along with decreased serum albumin levels, compared to controls. Additionally, compared to controls, there was a rise in the gene expression of TGF-β, Smad, collagen, α-SMA, MAPK, β-catenin, and GSK-3B, while the gene expression of CBS is decreased. The biochemical parameters indicated above were greatly improved by BMSCs pretreated with H2S, and the liver sections produced from this group demonstrated a notable improvement in histopathology. Conclusion: The study investigated and demonstrated how NaHS affected the efficacy of BMSC therapy in rats with CCl4-induced liver fibrosis.