Renoprotective effects of megadose vitamin C on cisplatin-induced kidney injury

Abstract

Cisplatin (CDDP)-induced nephrotoxicity is mediated via oxidative stress and may be alleviated using antioxidant activity. Although megadose of vitamin C may cause oxalate nephropathy and apoptosis, the antioxidant effect of vitamin C may be beneficial when given along with CDDP. The objective of this study was to investigate the renoprotective effects of megadose vitamin C on rats receiving CDDP. Rats were divided into 4 groups: group 1, control rats (CONT); group 2, vitamin C-treated rats (VIT C); group 3, CDDP-treated rats (CDDP) and group 4, CDDP + vitamin C-treated rats (CDDP + VIT C). Vitamin C (1000 mg/kg) was given intravenously to the VIT C and CDDP + VIT C groups while CDDP (6 mg/kg) was injected intraperitoneally into the CDDP and CDDP + VIT C groups. Renal function, oxidative stress, apoptosis and histopathology were investigated. At 5 days after injection, CDDP caused renal impairment as shown by significant increases in plasma concentrations of creatinine (PCr), urea nitrogen (PUN), urinary excretion of electrolytes (Na+, K+ and Cl-) and protein (P<0.05). Plasma malondialdehyde (P-MDA) and urinary MDA and creatinine ratio (U-MDA/Cr) were also increased (P<0.05). Kidney PCR products of antiapoptosis/proapoptosis (Bcl-2/Bax) were reduced by CDDP while histopathologic results showed severe massive tubular necrosis. Giving megadose vitamin C along with CDDP showed improvement on all renal function parameters and oxidative stress parameters except proteinuria. The vitamin C caused improvement on tubular cell lesions, but did not alter the Bcl-2/Bax level. It is concluded that megadose vitamin C can provide protection against CDDP-induced kidney injury by antioxidant activity.