title: Combination of Sitagliptin and Silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats.
abstract: Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl4) rat model. Male albino rats received intraperitoneal injections of CCl4three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100mg/kg) or Silymarin (100mg/kg) or their combination during the 7 weeks of intoxication. Hepatic fibrotic changes were evaluated by measuring hepatic enzymes (ALT, AST, ALP, and GGT) and markers of fibrosis (transforming growth factor β1 (TGF-β1), tissue 4-hydroxyproline level, histopathological score), oxidative stress (MDA, GSH, and NOx levels), inflammation (interleukin-6) as well as markers of HSCs activation (α-smooth muscle actin (α-SMA) expression). The injected rats with CCl4for 7 weeks resulted in a marked elevation of hepatic fibrotic changes and reduction of GSH level, while the combination therapy showed a significant decrease in the former one and a significant increase in the later. In conclusion, this study shows that the combination therapy is more beneficial than monotherapy in ameliorating liver fibrosis in rats. Our findings suggest that Sitagliptin alone or in combination with Silymarin may introduce a new strategy for treating liver fibrosis in humans.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
authors.forename: Samia Salem
authors.initials: SS
authors.lastname: Sokar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
authors.forename: Magda El-Sayed
authors.initials: ME
authors.lastname: El-Sayad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: maielsaid89@yahoo.com.
authors.forename: Mai El-Sayed
authors.initials: ME
authors.lastname: Ghoneim
authors.affiliation: Department of Pathology, Faculty of Medicine, El-Mansoura University, El-Mansoura, Egypt.
authors.forename: Abdelhadi Mohamed
authors.initials: AM
authors.lastname: Shebl
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D012838:Silymarin / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D020011:Protective Agents; D012838:Silymarin; D005978:Glutathione; D000068900:Sitagliptin Phosphate
keywords: Carbon tetrachloride; Liver fibrosis; Silymarin; Sitagliptin