Doxorubicin-induced Nephrotoxicity Model in Wistar rats: Characterization of Biochemical Parameters, Histological and Immunohistochemical assessment

Abstract

This study characterizes the doxorubicin (DXR)-induced nephrotoxicity model in Wistar rats in terms of biochemical, histological, and immunohistochemical assessments, to provide a methodological reference model to investigate potential nephroprotective therapeutics. The experiments were carried out using four groups of healthy male Wistar rats (six rats per group) administered with a single intraperitoneal dose of normal saline (vehicle group) and DXR at 17, 20, and 23 mg/kg doses, respectively. The rats were sacrificed under anaesthesia on the seventh day after DXR administration and blood, urine, and kidney tissues were collected for investigations. The DXR dose of 17 mg/kg showed mild changes in biochemical parameters, whereas 23 mg/kg resulted in increased mortality (33%). Serum concentrations of creatinine, urea nitrogen, β2-microglobulin, urine concentrations of total protein, creatinine, and urea increased with the increased dose of DXR while serum concentrations of total protein and albumin decreased (p<0.05). Assessment of histopathology revealed the features of acute tubular injury and immunohistochemical studies revealed increased apoptosis and inflammatory changes. Based on the findings, the DXR dose of 20 mg/kg was selected as the optimal dose for the establishment of an acute nephrotoxicity model in Wistar rats to explore potential nephroprotective drug leads.