Attenuation of renal damage in type I diabetic rats by umbelliferone - a coumarin derivative

Abstract

Background: It is well known that diabetes is one of the non-communicable disease affecting a large population worldwide. When diabetes remains untreated or uncontrolled, it leads to further serious complications, affecting vital organs like eyes, kidney, heart, etc. The present study was designed to evaluate effects of umbelliferone, a phytochemical, in treatment of diabetic nephropathy.

Methods: Experimental model used was streptozotocin (55mg/kg, ip) induced diabetic nephropathy in male Sprague Dawley rats. After 28days of streptozotocin administration, diabetic animals were treated with umbelliferone at two dose levels, 20 and 40mg/kg for next 28days.

Results: The results of the study showed that umbelliferone treatment significantly decreased the elevated plasma creatinine and blood urea nitrogen level while significantly increased the total protein and albumin level in diabetic animals. Creatinine clearance was improved in umbelliferone treated animals. Renal oxidative stress was decreased in umbelliferone treated animals significantly. Histopathological study of the kidney was carried out by specific stains like Hematoxylin-Eosin, Periodic Acid Schiff and Masson Trichrome stain. The sections of the kidney showed that umbelliferone treatment decreased the glomerular damage, mesangial matrix expansion as well as the renal fibrosis. Determination of renal transforming growth factor beta one (TGF-β1) expression by immunohistochemical analysis, western blotting and circulating TGF-β1 by ELISA assay showed that umbelliferone decreased the renal tissue and circulating TGF-β1 level.

Conclusion: Umbelliferone treatment can significantly reduce the diabetes induced renal damage and can improve the pathological conditions related to the diabetic nephropathy by down regulation of TGF-β.

Keywords: Diabetic nephropathy; Immunohistochemistry; Mesangial matrix index; Streptozotocin; TGF-β; Trichrome staining.