Induction of proteinuric chronic glomerular disease in the rat (Rattus norvegicus) by intracardiac injection of doxorubicin hydrochloride

Adriamycin nephropathy (AN) is a widely used nonimmune-mediated rat model o f proteinuric chronic glomerular disease and is usually induced by a single intravenous injection of doxorubicin hydrochloride (DX) into the tail vein . However, this route can be associated with local skin necrosis and variab ility in disease induction and poses an occupational hazard to the investig ator. Here we describe a simple technique of administering DX (1.7 mg) to k etamine:xylazine-sedated adult male Wistar rats (mean +/- 1 standard deviat ion, 238 8 g; n = 28) by using a single substernal intracardiac injection. The procedure was associated with minimal morbidity and mortality (1 death related to anesthesia). By day 21, severe nephrotic syndrome with effacemen t of glomerular epithelial cell foot processes and diffuse cortical tubuloi nterstitial injury was induced in all animals. Therefore, intracardiac inje ction of DX is a safe and consistent method of inducing AN in the rat and p rovides an alternative to the tail-vein route.