“Study of the Potential Anti-Fibrotic Effect of Linagliptin in Obese Diabetic Rats”

Abstract

The current study investigated the potential effect of linagliptin in preventing the pathological progression of liver fibrosis in HFD and STZ-induced diabetic rats and the underlying mechanism behind it. A pilot study was conducted for selecting linagliptin anti-diabetic dose; rats were randomly allocated into five groups each with six rats and treated orally for seven days as follows; Group 1: served as control and received vehicle 1% CMC. Group 2: served as diabetic model injected once IP with STZ (30 mg/kg) then received 1% CMC. Groups 3, 4, 5: diabetic rats received linagliptin 1, 3, and 6 mg/kg, respectively. After choosing 6 mg/kg as the optimum antidiabetic dose, the mechanistic study was carried out; the rat model of liver fibrosis with T2DM was established as follows; rats were fed a high-fat high sucrose diet (10% sucrose, 10% lard stearin, 2% cholesterin and 0.5% bile acid) for 28 days then injected once IP with STZ (30 mg/kg). After diabetes conformation; all diabetic rats were constantly fed HFD (10% lard stearin, 2% cholesterin, and 0.5% bile acid) until day 60. Rats were distributed randomly into four groups each with six rats and treated for 28 days as follows; Group 1, 2: control rats and fibrosis model, respectively, each received vehicle 1% CMC. Group 3: fibrotic rats challenged with linagliptin (6 mg/kg). Group 4: normal rats, received linagliptin (6 mg/kg). At the end of the experiment, rats were anesthetized by thiopental injection, blood samples were allowed to clot for 30 minutes before centrifugation. The serum was then collected and stored at -80 0C until further processing. The liver was dissected out in full depth and kept in 10% formalin for immunohistochemical and histopathological examination, other specimens were snap-frozen in liquid nitrogen and stored at -80 0C for gene expression, western blot, and biochemical analysis.