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Shvoong Home>Medicine & Health>RENOPROTECTIVE EFFECTS OF ENDOTHELIN RECEPTOR ANTAGONIST BOSENTAN ON DIABETIC RATS Review

RENOPROTECTIVE EFFECTS OF ENDOTHELIN RECEPTOR ANTAGONIST BOSENTAN ON DIABETIC RATS

Article Review   by:TsingHua     Original Authors: CHINESE JOURNAL OF NEPHROLOGY; DIALYSIS & TRANSPLANTATION
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To investigate the effects of endothelin receptor antagonist bosentan on the progression of renal injury in diabetic SD rat. METHODOLOGY 18 male SD rats(150~180g,8 weeks old)were included in the study.They were divided into 3 groups at random:untreated diabetic group(DM group, n =6),bosentan treated diabetic group(DM-B group, n =6)and normal control group (SD group, n =6).Diabetic rats were induced by intraperitoneal Streptozotocin injection(65 mg/kg)at one dose,and then divided into DM group and DM-B group.The DM-B group was given Bosentan 100 mg/(kg·d) by gavage for 4 weeks, while the DM and SD groups were given sterile water only.At the end of the fourth week,all rats fasted for 16 hours and 24 hours urine samples were collected.Under anestheization with 3% intraperitoneal chloral hydrate,a polyethylene(PE-50)catheter was applied to measure,mean arterial pressure(MAP)and to sample arterial blood at the rat′s right common carotid artery.Body weight,kidney weight,urinary protein excretion,creatinine clearance,circulating and renal endothelin were detected.Furthermore,the protein expression of renal matrix components,type Ⅳ collagen and laminin,as well as that of transforming growth factor β 1(TGF-β 1)were determined by immunohistochemistry and Western blot analysis.
RESULTS Untreated diabetic rats(DM group)had enhanced urinary protein excretion(68 2±0 34 mg/24h)and creatinine clearance(1 38±0 35ml/min)than those in normal group(14 68±2 01mg/24h,0 74±0 11ml/min, P <0 001,respectively).In DM group,immuno-histochemistry analysis showed over-expression of type Ⅳ collagen,laminin and TGF-β1.The change of TGF-β1 was further determined by Western blot method(1 97-folds higher than normal ones, P <0 01).Bosentan not only normalized urinary protein(28 2±3 60 mg/24h, P >0 05 vs .normal control)and creatinine clearance(1 13±0 31ml/min, P >0 05 vs .normal control),but also decreased the type Ⅳ collagen and laminin accumulation in the kidney.The expression of TGF-β1 in the kidney was significantly inhibited by 53 5% at the same time( P <0 01 vs. untreated diabetic rats). CONCLUSION Bosentan improves renal function by decreasing the extracellular matrix accumulation and TGF-β1 expression in kidney in diabetic rat,thus provide a new therapeutic approach to diabetic nephropathy.
Published: July 30, 2000   
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