[Effect of febuxostat on epithelial-to-mesenchymal transition of kidney tubules, serum interleukin-6 and transforming growth factor ß(1) in hyperuricemic rats].

ABSTRACT

Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)ß(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks. Rats in OF group and OB group were given either febuxostat or benbromarone starting with oteracil potassium, and rats in NC group was given saline only. Blood samples were taken before, and at the end of 4 and 8 weeks of the treatments and serum uric acid, creatinine, blood usea nitrogen(BUN), IL-6 and TGFß(1) contents were measured at each time point. Renal pathological changes were observed via HE and Masson staining, and the expression of α-SMA and E-cadherin were detected by immunohistochemistry. Results: Compared with those in NC group, the levels of serum uric acid, creatinine, BUN, IL-6 and TGFß(1) in the another three groups were increased significantly (all P<0.01). However, the IL-6 and TGFß(1) contents in OF group were much lower than those in OP group (P<0.01). HE and Masson staining showed that OF group had less damage and tubulointerstitial fibrosis than OP group and OB group (P<0.01). Moreover, the expression of α-SMA was significantly down-regulated (P<0.01) and that of E-cadherin was significantly up-regulated in OF group compared with those in OP group. Conclusion: Febuxostat treatment significantly inhibited EMT and reduced the levels of IL-6 and TGFß(1) in hyperuricemia rats.