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

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. 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. 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. 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. Cholestasis results in disorders of bile flow. Prolonged cholestasis can lead to tissue fibrosis and severe liver cirrhosis. High concentrations of bile acids cause directly damage the liver, leading to hepatocyte apoptosis and liver inflammation. Oxidative stress, lipid peroxidation, and an increase in malondialdehyde (MDA) levels occur in the liver following bile duct ligation (BDL). Herbal compounds can be used as alternatives or additions to conventional medications for preventing or treating of liver cirrhosis. D-limonene, an antioxidant, at doses of 50 and 100 mg/kg reduces oxidative stress, inflammation, fibrosis, bile duct proliferation, and hepatocellular necrosis in the BDL model.