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Nephroprotective effect of bosentan in diabetic rats
Alessandro Cosenzi1, Elena Bernobich, Roberto Trevisan
1Dipartimento di Medicina Clinica e Neurologia, University of Trieste, Trieste, Italy. a.cosenzi@fmc.units.it
Abstract:
Previous studies have suggested that endothelins could be involved in the pathogenesis of target organ damage in diabetes. The aim of this study was to evaluate the possible protective effect of Bosentan, an antagonist of endothelin receptor, on the kidney of diabetic rats. The study comprised a control group of 10 WKY rats and a group of 22 WKY rats in which diabetes was induced by streptozotocin i.v.; 10 rats were the control group. Diabetic rats received insulin and mean blood glucose was approximately mS 400 mg/dl throughout the study; they were divided into two groups: 11 rats received Bosentan 100 mg/kg/die by gastric gavage and 11 received vehicle for 1 month. Twenty-four hour urine collection was performed before and at the end of the study. Urinary protein excretion rate was expressed as microg urinary protein/mg urinary creatinine. The renal collagen I, fibronectin, and TGFbeta were evaluated by means of immunochemistry. The statistical analysis of the results demonstrates that Bosentan has prevented the increase in urinary protein excretion and that of renal immunoreactive collagen I, fibronectin, and TGFbeta induced by diabetes without reducing blood pressure. This study suggests a new clinical application for the antagonists of endothelin receptors.
Insights
Bosentan, an endothelin receptor antagonist, protected diabetic rat kidneys from damage by reducing urinary protein and specific protein markers. This suggests a new use for endothelin receptor antagonists in managing diabetic kidney disease.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Endothelins are implicated in diabetic target organ damage.
- Endothelin receptor antagonists may offer protective effects.
- Diabetes mellitus can lead to significant kidney complications.
Purpose of the Study:
- To investigate the renoprotective effects of Bosentan, an endothelin receptor antagonist, in a rat model of diabetes.
- To assess the impact of Bosentan on diabetic nephropathy markers.
Main Methods:
- Diabetes was induced in WKY rats using streptozotocin.
- Diabetic rats were treated with Bosentan (100 mg/kg/day) or vehicle for one month.
- Evaluated 24-hour urinary protein excretion and renal expression of collagen I, fibronectin, and TGF-β via immunohistochemistry.
Main Results:
- Bosentan significantly reduced urinary protein excretion in diabetic rats.
- Bosentan prevented the diabetes-induced increase in renal collagen I, fibronectin, and TGF-β.
- These protective effects were observed without a reduction in blood pressure.
Conclusions:
- Bosentan demonstrates renoprotective properties in diabetic rats, independent of blood pressure.
- Targeting endothelin receptors may be a viable strategy for preventing diabetic kidney disease.
- Endothelin receptor antagonists may represent a novel therapeutic approach for diabetic nephropathy.
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