Histopathological and biochemical assessment of kidney damage in albino wistar rats treated with cytotoxic platinum compounds in combination with 5-FU

Abstract

Kidney cells damage and subsequent renal adverse effects with oxaliplatin are less reported phenomena, whereas cisplatin (CDDP, first generation platinum compound) has therapeutic limitations due to renal toxicity. This experimental study reports oxaliplatin (third generation platinum compound) induced direct damage in rat kidney tissues and alterations in renal biochemical profile. Oxaliplatin was administered in albino wistar rats with 5-FU (5 Fluorouracil) to mimic as model of FOLFOX, the mainstay chemotherapeutic regimen in colorectal cancer (CRC). This study reports changes in renal biochemical profile (serum creatinine and urea) in rats treated in different treatment groups with cisplatin, oxaliplatin, 5-FU, cisplatin+5-FU and oxaliplatin+5-FU which are compared with group of rats treated with normal saline (control group). Subjective renal toxicity in tissues was compared among rats treated with oxaliplatin alone and cisplatin, with and without 5-FU by light microscopy. Cast formation, medial hypertrophy of the vessel wall, vacuolization and necrosis was seen in kidney tissues of oxaliplatin treated rat. Changes in serum creatinine well-above diagnostic risk levels were noted. Apparent tubular degenerative sequence associated with vacuolization and cast formation was observed in 5-FU treated rats. Kidney damage ensued after treatment with 5-FU and oxaliplatin are slightly comparable to massive tubular damages, hemorrhage, casts and vacuolization along with multiple foci of alterations induced by cisplatin.