Abstract: TH-PO408

The Role of Nrf2/HO-1 Signaling Pathway in Mild Hyperuricemia Promoting the Progress of CKD

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Zhao, Zhihong, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
  • Zhou, Qin, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
  • Zou, Hequn, The 3rd Affiliated Hospital of Southern Medical University, Guangzhou, China
Background

Previously it was believed that mild hyperuricemia had no pathogenic effect. However recently it is recognized that mild hyperuricemia can accelerate the progression of chronic kidney disease. The aim of this study was to investigate the role of Nrf2/HO-1 signaling pathway in mild hyperuricemia promoting the progress of chronic kidney disease in a rat model of 5/6 nephrectomy.

Methods

Rats were randomely dividided into five groups (n=8 in each group): Control Group, RK Group (5/6 nephrectomy), OA Group (750mg/kg/d oxonic acid treatment for 6 weeks), RK+OA Group and RK+OA+SFN Group (5mg/kg/d sulforaphane treatment for 6 weeks). Renal function, malondialdehyde (MDA) level, and SOD activity were determinated. Renal pathology was observed by light microscope. Western blot and immunohistochemical assays were used to test the expression of Nrf2, HO-1, P38/p-P38, ERK/p-ERK protein.

Results

Compared with the controls, the level of serum uric acid was increased in the OA Group and RK+OA Group respectively (P<0.05), but not significantly changed in the RK Group (P>0.05). Compared with RK Group, either the level of blood urea nitrogen (BUN), serum creatinine (Scr), 24-h urinary protein output or MDA was increased, the SOD activity was decreased in the RK+OA group(P<0.05). Compared with the RK+OA group, those blood and urine biochemical indices were decreased, MDA level was decreased, the SOD activity was increased, and the renal histological damage was ameliorated in the RK+OA+SFN group (P<0.05). The expression of Nrf2 nuclear protein and HO-1 protein were decreased in RK+OA group compared with either control or RK group, SFN increased the expression of Nrf2 and HO-1 in RK+OA+SFN group, the expression of P-p38 protein and p-ERK protein were decreased (P<0.05).

Conclusion

It is indicated by the results of our present study that mild hyperuricemia accelerated the progression of chronic kidney disease. Furthermore it is suggested by our results that the mechanism of mild hyperuricemia in inducing renal damage might be promoting oxidative stress by inactivating Nrf2/HO-1 signal pathway. It is also suggested that SFN could attenuate the renal injury induced by mild hyperuricemia and its mechanism might be allivateing the oxidative stress injury through activating Nrf2/HO-1 signal pathway. SFN may also affect the activity of ERK signaltransduction pathway.

Funding

  • Government Support - Non-U.S.