Protective Effects And Mechanism Of 5-ASA On Paraquat Toxicity In Rat Kidney

Objective: To investigate the protective effect and mechanism of 5-ASA on acute renal injury induced by paraquat.Methods: 144 male SD rats were randomly divided into 4 groups: blank control group(N group),5-ASA control group(A group),PQ poisoning group(P group)and 5-ASA treatment group(P+A group);P group and P+A group were treated with 2% PQ solution by intraperitoneal injection to establish acute renal injury model.The other two groups were treated with saline by intraperitoneal injection.After 2 hours of intraperitoneal injection,A group and P+A group were respectively administered with 5-ASA(75mg/kg)by means of gavage once a day.Meanwhile,P group and N group were administered with saline by means of gavage once a day.Then the rats were sacrificed at five different time points(6h,12 h,24h,72 h,168h)for cardiac blood collection which can be used to detect the changes of Scr,BUN,SOD,CAT,GSH and MDA.In addition,Hematein Eosin Staining were applied to observe the kidney-tissue image and Western blot were applied to evaluate the expression of Nrf2 and HO-1.Results: 1.Compared with P group,the morphological changes and pathological damage of P+A group was mitigated after poisioning.A group and N group did not appear poisoning performance.2.The values of BUN in P group were significantly higher than those in other groups after 12 h,in 12 h,24h,72 h,168h elevated significantly(P<0.01).The values of Cr in P group were significantly higher than that in N group after 24 h,in 12 h,24h,72 h,168h elevated significantly(P<0.05).The values of BUN in P+A group decreased in 12 h,24h,72 h,168h in comparison with P group(P<0.01).The values of Cr were lower than that in P group at 24 h and 72h(P<0.01).3.Oxidative damage and inflammatory response markers: The activities of SOD,MDA,CAT,GSH in both A group and N group remained at relatively stable level at each time point.The activities of SOD,GSH and CAT in P group were significantly lower than those in N group at 12 h,24h,72 h,168h after poisioning(P<0.05).The activities of SOD,GSH and CAT in P+A group increased significantly in comparison with P group at 24 h,72h,168h(P<0.05).MDA levels in P group began to increase at 6h,which increased significantly at 12 h,24h,72 h and 168 h.Compared with p group,MDA levels in P+A group decreased obviously at 24 h,72h and 168h(P<0.05).4.Westernblot shows that the protein expressions of Nrf2 and HO-1 in P group kidney were higher than those in N group kidney after poisioning at 24 h and 72 h,especially at 24h(P<0.05).The protein expressions of Nrf2 and HO-1 in P+A group kidney were significantly higher than those in P group kidney at 24 h and 72h(P<0.01).The protein expressions of Nrf2 and HO-1 in A group kidney were higher than those in N group(P<0.01).Conclusion:5-ASA attenuates the acute renal injury caused by PQ,the mechanism of which may be related to the activation of Nrf2-ARE signaling pathway.