Korean Journal of Nephrology 2000;19(5):926-933.

일측신 절제 쥐에서 급성 Cyclosporine A 신독성에 관한 비타민 C와 E의 예방적 효과 (Protective Effect of Vitamin C and E in Acute Cyclosporine A Nephrotoxicity in Heminephrectomized Rats)

최광해(Gwang Hae Choi),이은실(Eun Sil Lee),박용훈(Yong Hoon Park),김용진(Yong Jin Kim),박종민(Jong Min Park)

Abstract

Purpose
It has been reported that there is close association between cyclsoporine nephrotoxicity and lipid peroxidation. This study was performed to evaluate the protective effects of vitamin C and E as oxygen free radical scavenger. Method: Sprague Dawley male rates were divided into 3 groups: Group I(the control group), group II(injection of only CsA 50mg/kg of day intraperitoneally), and group III(CsA 50mg/kg of day intraperitoneally with vitamin E 10mg/kg of day and vitamin C 250mg/kg of day intramuscularly). The all of Sprague Dawley male rats were heminephrectomized at seven days prior to injection of CsA for nephrotoxicity more effectively. On the 6th day of the experiment, all rats were placed in a metabolic cage to collect urine samples to measure 24-hours urine creatinine, α-glutathione transferase. On the 7th day upon sacrifice of the experimental animals, blood sampling for measurement of blood CsA level and serum creatinine and nephrectomy for morphological study and malondialdehyde obtained from fractionation of the mitochondria were performed. Results: Final creatinine clearance of group I and III was not significantly decreased compared to initial creatinine clearance, but creatinine clearance of group II was significantly decreased(initial vs final: 2.15±1.24 vs 0.55±0.42mL/min/100g p<0.05). Urine α-glutathione transferase and renal cortical malondialdehyde of group II were significantly increased compared to group I but in group III, there were no significant increasement in comparison with group I. Histological change, CsA induced nephrotoxicity, characterized by the presence of a large number of lysosomes and derangement of mitochondria in the tubular epithelium but this change was diminished by administration of vitamin C and E. Conclusions: The result of this study provide the evidence that CsA induced nephrotoxicity is associated with lipid peroxidation. Based on this finding, we proposed that vitamin C and E, oxygen radical scavenger, may be effective in attenuating CsA induced nephrotoxicity in this setting.