ANTIAPOPTOTIC EFFECS OF CATECHIN AND GEMIGLIPTIN ON TACROLIMUS-INDUCED RENAL INJURY IN MICE

Abstract Background and Aims The aim of this study was to investigate the anti-apoptotic effects of catechin (CA) and dipeptidyl peptidase IV (DPP IV) inhibitor gemigliptin on tacrolimus (TAC)-induced nephropathy in mice. Method The mice (n=30) were divided into 5 groups (n=6/group); control group were intraperitoneally (IP) injected 0.9% saline, TAC group were IP injected TAC 2.5 mg/kg, DPP IV inhibitor group were given in addition gemigliptin 20 mg/kg (G20) by oral gavage. TAC-CA group were given TAC by IP injection and CA 100 mg/kg by subcutaneous injection. TAC-TA-G20 group were given with same dosages. Results The 24 hours urine protein amounts were significantly increased in TAC group (46.1±10.9mg/day) compared to control group (11.3 ±4.4mg/day) and significantly decreased in TAC-CA-G20group (13.1 ±5.9mg/day, P <0.01) compared to TAC group. Serum creatinine levels were significantly increased in TAC group (1.03 ± 0.26 mg/dL) compared to control group (0.17 ± 0.02 mg/day) and significantly decreased in TAC-CA-G20group (0.23 ± 0.05 mg/day, p=0.008) compared to TAC group. In Western blot analysis of apoptotic protein, the BCL-2 protein expression by TAC was significantly suppressed by CA and gemigliptin injection but, the p53 protein expression by TAC was significantly resolved by CA and DPP IV inhibitor. There are proximal tubular edema and mild interstitial inflammation in the kidney of mice after TAC injection but no significant pathologic changes by CA injection and DPP IV inhibitor injected group. Conclusion Catechin and DPP IV inhibitor gemigliptin treatment has beneficial antiapoptotic effects on acute TAC-induced renal injury in mice.