Effect of Short-Chain Fatty Acids In Vivo on the Treatment of CCL₄-Induced Hepatic Fibrosis

Background/Objectives: Hepatic fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition in the liver, which may progress to cirrhosis and liver failure. Short-chain fatty acids (SCFAs) have demonstrated anti-inflammatory and anti-fibrotic properties; however, their therapeutic potential in hepatic fibrosis remains incompletely understood. This study aimed to evaluate the effects of acetate, propionate, and butyrate on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in Balb/C mice. Methods: Hepatic fibrosis was induced in Balb/C mice using CCl₄, and the animals were treated with acetate, propionate, or butyrate administered via drinking water for four weeks. Biochemical parameters, histological alterations, and the expression of fibrogenic and inflammatory markers were evaluated and compared with a silymarin-treated group. Results: Treatment with SCFAs significantly reduced serum transaminase levels (AST and ALT) compared to the untreated fibrotic group. Histological analyses demonstrated the preservation of hepatic architecture and reduced inflammatory infiltrates, particularly in the butyrate-treated group. In addition, SCFAs significantly decreased the gene and protein expression of fibrogenic markers (ACTA2 and COL1A1) and inflammatory markers (NOS1, NF-κB, and IL-10), with propionate showing the most pronounced effects. Overall, the therapeutic effects observed with SCFAs were comparable or superior to those obtained with silymarin treatment. Conclusions: The findings suggest that SCFAs, especially butyrate and propionate, exert hepatoprotective, anti-inflammatory, and anti-fibrotic effects in CCl₄-induced hepatic fibrosis. These compounds represent promising therapeutic candidates for the treatment of liver fibrosis.