title: Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy.
abstract: Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Rania A
authors.initials: RA
authors.lastname: Elrashidy
authors.forename: Mervat E
authors.initials: ME
authors.lastname: Asker
authors.forename: Hoda E
authors.initials: HE
authors.lastname: Mohamed
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications*; D005355:Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology; D006331:Heart Diseases / Q000188:drug therapy* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000077205:Pioglitazone; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008055:Lipids; D045162:Thiazolidinediones; D003404:Creatinine; D000077205:Pioglitazone