Dose Response of Carboplatin‐Induced Nephrotoxicity in Rats

Abstract

Carboplatin, a second-generation platinum-containing anticancer drug, is currently being used against a variety of cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. However, the biochemical mechanism of carboplatin-induced renal injury has not been well studied. This study investigated the dose response of carboplatin-induced changes in endogenous antioxidants, lipid peroxidation and platinum content in rat kidney. Male Wistar rats (250-300 g) were divided into five groups and treated as follows: (1) control (saline, intraperitoneally); (2) carboplatin (64 mg/kg, intraperitoneally); (3) carboplatin (128 mg/kg, intraperitoneally); (4) carboplatin (192 mg/kg, intraperitoneally); and (5) carboplatin (256 mg/kg, intraperitoneally). The animals were sacrificed four days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine and blood urea nitrogen levels were increased significantly in response to carboplatin in a dose-dependent manner. Renal superoxide dismutase and catalase activities were decreased significantly due to carboplatin at dosages of 128 mg/kg and above. The protein expressions of renal copper/zinc-superoxide dismutase and manganese-superoxide dismutase significantly depleted after carboplatin. Carboplatin (192 and 256 mg/kg) significantly increased lipid peroxidation (malondialdehyde concentration) in rat kidneys. Carboplatin dose-dependently increased the renal platinum concentration, with significance at dosages of 128 mg/kg and above. Carboplatin (256 mg/kg) significantly increased renal xanthine oxidase activity, while ratio of reduced to oxidized glutathione depleted significantly. The data suggested that carboplatin caused dose-dependent oxidative renal injury, as evidenced by renal antioxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine and blood urea nitrogen levels in rats.

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Production of Functional Fermented Milk Beverages Supplemented with Pomegranate Peel Extract and Probiotic Lactic Acid Bacteria

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Carboplatin-induced Fanconi-like syndrome in rats: Amelioration by pentoxifylline

“…This is one of the dose-limiting adverse effects related to clinical use of carboplatin. Several studies have shown that carboplatin administration can lead to dose-dependent nephrotoxicity in rodents and human beings specifically leading to acute tubular necrosis (Haschke et al, 2010;Husain et al, 2002Husain et al, , 2004. We have tried to corroborate these findings in rats treated with an overdose of carboplatin and tried to correlate carboplatin-induced renal damage to that of impairment of renal function observed in experimentally induced Fanconilike syndrome.…”