title: Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.
abstract: Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.
authors: Department of Pharmacology, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
authors: Rowaida
authors: R
authors: Refaat
authors: Department of Pharmacology, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
authors: Ahmed
authors: A
authors: Sakr
authors: Department of Pharmacology, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
authors: Mona
authors: M
authors: Salama
authors: Department of Pathology, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
authors: Ashgan
authors: A
authors: El Sarha
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000503:physiopathology; D000077205:Pioglitazone; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D014508:Urea / Q000097:blood; D000077597:Vildagliptin
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D045162:Thiazolidinediones; D014508:Urea; D003404:Creatinine; D000077597:Vildagliptin; D000218:Adamantane; D000077205:Pioglitazone
keywords: Type 2 diabetes; insulin resistance; pioglitazone; vildagliptin