Study of urinary biomarkers for nephrotoxicity in wistar rats

Abstract

Nephrotoxicity is the second most persistent cause of drug withdrawal. In this study, we have determined the presence of nephrotoxic biomarkers in experimentally-induced site specific kidney injury. This study include measurement urinary clusterin, microalbumin, traditional serum nephrotoxic biomarkers (creatinine, urea, albumin, total protein), qualititative urine analysis and histopathological examination of kidney in rat models treated with carboplatin and ibuprofen- induced renal tubular injury. Female wistar rats were divided into four groups of six animals each were treated as follows: (1) Normal saline (O mg kg-1 intraperitoneally) (2) Carboplatin (250 mg kg-1, intraperitoneally) (3) 0.5% Carboxy methyl cellulose (O mg kg-1, orally) (4) Ibuprofen (800 mg kg-1, orally). Blood urea levels increased significantly in response to carboplatin and ibuprofen treated rats indicating potential nephrotoxicity. In carboplatin and ibuprofen treated rats, urinary clusterin was dramatically increased indicating dysfunction of proximal tubule. Additionally carboplatin and ibuprofen treated rats showed proteinuria, microalbuminuria and hypoalbuminemia revealing dysfunction of either distal tubule or loop of henle. The data suggested potential proximal tubular damage alongwith damage to distal tubule and loop of henle in presence of carboplatin and ibuprofen. Therefore, combinatorial measurement of clusterin and microalbumin with other nephrotoxic biomarkers such as kidney injury molecule-1, Cystatin C, Beta-2 microalbumin and trefoil factor 3 might work as powerful tool for highly effective screening of nephrotoxicity. © 2011 Academic Journals Inc.