Abstract / Summary
Abstract Cholestasis, caused by impaired bile flow, can progress to severe liver injury and fibrosis. Oxidative stress and inflammation are major drivers of this process. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor used for hyperglycemia, has also been reported to show antioxidant and anti-inflammatory properties. This study evaluated whether sitagliptin can attenuate bile duct ligation (BDL)-induced liver fibrosis in rats and examined related mechanisms. 35 male Wistar rats were randomized into five groups: sham, BDL, and BDL treated with sitagliptin at 10, 50, or 100 mg/kg. After BDL surgery under anesthesia, rats received saline or sitagliptin by oral gavage for 14 days. Serum and liver tissues were collected for biochemical and molecular assessment. Liver injury were evaluated using H&E and Masson’s trichrome staining. BDL increased serum alkaline phosphatase, lactate dehydrogenase, and total bilirubin, and elevated hepatic oxidative and inflammatory markers, including MDA, TNF-α, TGF-β, and Sestrin2, along with higher hydroxyproline content and fibrosis scores. Antioxidant defenses (SOD activity, total antioxidant capacity, and Nrf2) were decreased. Sitagliptin reversed these changes, reducing oxidative stress and inflammation and improving antioxidant responses, with some effects more evident at 10 mg/kg. In conclusion, sitagliptin mitigated BDL-induced fibrosis by suppressing oxidative stress and inflammatory signaling.