The Protective Effects And The Related Mechanisms Of EGCG On Kidney Injure Rat Induced By Cisplatin

ObjectiveThe protective effects of epigallocatechingallate(EGCG)on the rats kidney oxidative stress injure induced by cisplatin were researched and mchanisms was explored initially,to investigate its related activation of Nrf2 / HO-1 pathway possible mechanisms.MethodsFifty male SD rats were randomly divided into: control group(C),kidney injure group(M),drug groups with decreasing EGCG dose of ED(EGCG 25 mg/kg),EZ(EGCG 50mg/kg),EG(EGCG 100mg/kg),according to their body weight.The 4 behind group were geiven intraperitoneal injection of cisplatin 7.5mg / kg to preparate a renal injury model,however the normal group were injected with same volume saline.Modeling day,the EGCG different dose intervention group were treated with different EGCG dose,however the control group and M group with the same volume of normal saline.This procedure was executed for consecutive 14 days.The rat kidney index was statisticed.The rat kidney tissue was also colored in the HE stain to observe the kidney injure.The serum traditional markers BUN(blood urea nitrogen)and Cr(creatinine)concentration was detected by kit method day 2 and day 14.The serum early marker Cys-c(cystatin C,Cystatin c)and the urine IL-18(interleukin-18),KIM-1(kidney injury molecule 1)concentration were also tested by elisa method day 2 and day 14.The purpose was to evaluation the role of EGCG used by the sensitive and traditional renal injury markers.To research the impact of EGCG on oxidative stress capability and antioxidant capacity in the injuried renal cortex,the concentration of malondialdehyde(MDA),antioxidant enzyme systems glutathione(GSH),and the superoxide dismutase(SOD)activity in the renal cortex were detected by kit method.Detecting the antioxidant(cytoplasm Nrf2,nucleus Nrf2 and total HO-1)protein expression level in the renal cortex,aimed to explore whether EGCG could played an antioxidant protective effects on the rats kidney injure induced by cisplatin by activating the intracellular endogenous Nrf2 / HO-1 pathway.ResultsCompared with the control group,the kidney injury group(M)induced by cisplatin appeared food intake reduced,listlessness,body weight loss,curly arched,light hair color loss and other symptoms in 2-3 days.Compared with the kidney injury group,the EZ and EG administered groups reduced food intake,loss of light coat symptoms in a reduced degree and delayde time.Moreover,compared with the control group,the tubular dilation appeared in varying degrees,some of the tubular epithelial cell fell off because of degeneration and necrosis,and the basement membrane was bare in the kidney injured rats.Besides,a lot of red dye unstructured particulate matter and much of protein casts appeared in the renal tubular cavity in the kidney injure rats.After the intervention of distinctive doses of EGCG,the indicators mentioned above have improved.It could improve tubular epithelial cell degeneration,necrosis,basement membrane in the EZ and EG groups.It reduced particulate matter cavity red dye and unstructured protein tubular lumen tube type to alleviate the situation in the EZ and EG groups.compared with the vacant control group,the renal mass index increased significantly in the kidney injury group(P<0.01).Compared with the kidney injury group,the kidney index decreased in the EZ and EG groups(P<0.05).Compared with the control group,the serum BUN,Cr concentration did not change significantly in the model group rats in day 2(P>0.05),the serum Cys-c and urine IL-18,KIM-1 concentration was significantly higher in the model group rats in day 2(P<0.01).Compared with the kidney injury group,the serum Cys-c concentration decreased in the EZ and EG groups after 2 days administration,(P<0.05).After administration 14 days,compared with the kidney injury group,the serum Cr concentration decreased in the ED group,EZ group and EG group(P<0.05).Compared with the kidney injury group,the serum Cys-c concentration decreased in the ED and EZ groups(P<0.05),the serum Cys-c concentration decreased significantly in the EG group(P<0.01),the urine IL-18 concentration decreased in the EG group(P<0.05),the urine KIM-1 concentration decreased in the ED,EZ and EG groups(P<0.05).Compared with the control group,the renal cortex MDA concentration increased significantly in the injury group(P<0.01),the renal cortex GSH concentration and T-SOD activity reduced significantly(P<0.01).Compared with the kidney injury group,the renal cortex MDA concentration decreased in the EZ and EG groups(P<0.05);the renal cortex GSH concentration increased in the EZ and EG groups(P<0.05),the renal cortex T-SOD activity increased in the EG group(P<0.05).Compared with the control group,the cytoplasmic Nrf2 and nuclear Nrf2 levels of the renal cortex increased significantly(P<0.01),the HO-1 level of the renal cortex increased(P<0.05)in the kidney injury group.Compared with the kidney injury group,the renal cortex cytoplasmic Nrf2 decreased(P<0.05)in the EG group.Compared with the model group,a significant increase in nuclear Nrf2 level in the renal cortex appeared in the EZ and EG groups(P<0.01);Compared with the kidney injury group,the renal cortex total cellular HO-1 level increased in EZ group(P<0.05),the total cell content of HO-1 level in the renal cortex increased significantly in the EG group(P<0.01).ConclusionsSensitive and traditional markers of renal function were joint to edevaluate the role of EGCG,which showed that EGCG has a protective effect on renal damage rats induced by cisplatin.The mechanism might be related to activate the intracellular endogenous antioxidant Nrf2 / HO-1 pathway and started the body's own antioxidant defense system.