Anti-fibrotic and anti-inflammatory effects of D-limonene in improving liver cirrhosis induced by bile duct ligation in male rat.

BACKGROUND AND AIM: Liver fibrosis is one of the pathological consequences of several liver diseases that can lead to liver cirrhosis. Some anti-fibrotic drugs for liver fibrosis have not yet been clinically approved. The current study assesses the antioxidant properties of D-limonene (DL) on cholestatic liver damage induced by bile duct ligation (BDL) in rats. EXPERIMENTAL APPROACH: For this purpose, 36 male rats were randomly divided into six equal groups: Sham, BDL, BDL + 50 DL, BDL + 100 DL, 50 DL, and 100 DL. The rats underwent BDL surgery and were treated with DL for a duration of 28 days. Serum liver enzymes were measured, and liver tissue was examined for histopathological, biochemical, and gene expression studies. KEY FINDINGS: Treatment with DL, administered in two doses of 50 and 100 mg/kg, resulted in decreased levels of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, and γ-glutamyl transpeptidase (GGT). Additionally, it reduced the expression of caspase-3, TNF-alpha, and malondialdehyde, leading to a decrease in liver cell damage and liver fibrosis. Moreover, DL was found to increase the activity of antioxidant enzymes and glutathione levels in the BDL model. CONCLUSIONS: The results of this study suggest that DL could be considered a potential candidate for protecting the liver against cholestatic damage due to its anti-fibrotic and antioxidant properties.