사이클로스포린 유발성 신독성에 대한 green tea polyphenol의 예방 효과

Abstract

Purpose Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but use is frequently accompanied by severe nephrotoxicity. The causes for the renal toxicity of CyA have not fully elucidated. Recently, the interest of many researchers has been pointed to minimize these effects by pharmacological interventions. Green tea polyphenol, (-)-epigallocatechin 3-O-gallate (EGCG), has potent antioxidants. For the aims we tested whether the administration of green tea polyphenol prevents the development of CyA-induced nephrotoxicity. Method The rats (n=20) were divided into 4 groups (n=5/group); group 1 (control group)rats were intra peritoneal (IP) injected 0.9% saline solution, group 2 (CsA group) received CsA 30 mg/Kg body weight daily for 21days by IP injection, group 3 (CsA+L-NAME group) received ath the same dose above in addition to L-NAME 12 mmol/L daily by intramuscular injection. The group 4 (CsA + green tea polyphenol group) received CsA 30 mg/Kg body weight daily for 21days by IP injection in addition to green tea polyphenol 100mg/Kg by intramuscular injection. At last day, upon sacrifice of the rats, blood urea nitrogen (BUN), creatinine, potassium and aldosterone were measured and nephrectomy was done for morphological study, malondialdehyde and antioxidative enzyme analysis. Results There were significant increased seum urea nitrogen (BUN) (48.5±8.5 mg/dL), serum creatinine (1.1±0.60mg/dL), malondialdehyde (3.09±0.20nmol/mL protein) and serum aldosterone (10.2±3.5ng/dL) in group 2 compared to group 1(P<0.01). Serum BUN(1.10±0.082mg/dL,), serum creatinine(0.51±0.045mg/dL) and malodialdehyde (1.21±0.34nmol/mg protein) were significantly reduced in group 3 compared to group 2(p<0.01), but serum aldosterone and potassium levels were no change. Serum BUN(23.1±5.27mg/dL), serum creatinine(0.51±0.045mg/dL), malondialdehyde(0.89±0.32nmol/mg protein) and serum aldosterone(12.02±4.63 ng/dL) were significantly reduced in group 4 compared to group 2 (p<0.01), but serum potassium level was no changes. In the histologic examination, there were proximal tubular necroses and mild interstitial inflammation in the kidneys of rats in group 2 but no significant pathologic changes in group 4 and group3. Conclusion Green tea polyphenol protect against CyA induced nephrotoxicity in the rats.Reduction of oxidative stress and lipid peroxidation and aldosterone levels may be responsible for the protective effect of Green tea polyphenol on CyA-induced structural and functional alternations of the kidney.