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Effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes
- Source :
- European Journal of Pharmacology. 685:156-164
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.
- Subjects :
- Pathology
medicine.medical_specialty
Tetrazoles
Apoptosis
Mitochondria, Liver
Liver Cirrhosis, Experimental
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
Liver disease
Non-alcoholic Fatty Liver Disease
Internal medicine
Nonalcoholic fatty liver disease
In Situ Nick-End Labeling
medicine
Animals
Respiratory function
Pharmacology
TUNEL assay
business.industry
Valine
medicine.disease
Streptozotocin
Rats
Fatty Liver
Endocrinology
Diabetes Mellitus, Type 2
Gene Expression Regulation
Valsartan
Disease Progression
Hepatocytes
Steatosis
business
Hepatic fibrosis
Angiotensin II Type 1 Receptor Blockers
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 685
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....219f9fc36cf65e0791c44f4abf3a34f3