RENAL OXIDATIVE STRESS AND APOPTOSIS IN RAT RECEIVING CISPLATIN AND MEGADOSE VITAMIN C

Abstract

The objectives of this study were to investigate the effects of megadose vitamin C in rats with cisplatin (CDDP) induced nephrotoxicity. Rats were divided into 4 groups as follows, group 1 (CONT), group 2 (vitamin C treated group; VIT C), group 3 (CDDP treated group; CDDP) and group 4 (CDDP + vitamin C treated groups; CDDP + VIT C). The vitamin C at the dose of 1000 mg/kg was given to the rats on day 1 in VIT C and CDDP + VIT C groups while CDDP was injected intraperitonealy at the dose of 6 mg/kg on day 1 in CDDP and CDDP + VIT C groups. The rats were subjected to renal function studies on one day before drug treatment (day 0) and 6 days after treatment (day 6). Blood and urine sampling were collected for measuring PUN and creatinine (Pcr) one day prior to renal clearance study in the metabolic cage. The GFR and fractional excretions of electrolytes were calculated. The oxidative stress markers, MDA, PC and TAS were measured in the plasma and urine while MDA, GSH and CAT were measured in the kidney. The results showed that at 6 day after CDDP administration, renal impairment as shown by significant reduction in GFR (P<0.05) with increased Pcr (P<0.05), PUN (P<0.05) and fractional excretion of electrolytes (Na+, K+ and Cl-) and protein (P<0.05) were apparent as compared to control without CDDP. In CDDP-treated rats given vitamin C (CDDP + VIT C group), the GFR was improved significantly as compared with CDDP group. The Pcr and PUN levels also reduced although they were not significant different than CDDP group. By measuring the oxidative stress parameters, the plasma MDA increased in CDDP group significantly (P<0.05) when compared with other groups. Urinary MDA/Cr also increased along with decreased TAS. The GFR value was correlated with PMDA, urinary MDA/Cr and urinary TAS. Giving vitamin C in CDDP-treated rats (CDDP + VIT C group) showed improved GFR and lower PMDA, urinary MDA/Cr with increased urinary TAS. However, the PCR products of antiapoptosis/proapoptosis (bcl-2/bax) which was reduced 6 days after CDDP was unchanged. These results suggest that CDDP cause severe glomerular and tubular damage, renal apotosis with enhanced renal oxidative stress. CDDP induced renal impairment may be mediated via renal oxidative damage. Giving megadose vitamin c in CDDP treated rats could alleviate the effects of CDDP on renal functions but not renal apoptosis via reduction in renal oxidative stress.