<i>N</i>-Acetylcysteine overcomes epalrestat-mediated increase of toxic 4-hydroxy-2-nonenal and potentiates the anti-arthritic effect of epalrestat in AIA model
Linna Wang, Baixiong Huang, Yaling Zeng, Jiujie Yang, Zhi Li, Jerome P. L. Ng, Xiongfei Xu, Lü Su, Xiaoyun Yun, Liqun Qu, Ruihong Chen, Weidan Luo, Yuping Wang, Chang Chen, Lijun Yang, Yuan Qing Qu, Wei Zhang, Joyce Tsz Wai Chan, Xingxia Wang, Betty Yuen Kwan Law, Simon Wing Fai Mok, Sookja Kim Chung, Vincent Kam Wai Wong
Abstract
-Acetylcysteine (NAC), an anti-oxidant, to AIA rats dramatically suppressed the production of 4-HNE, MDA and inflammatory cytokines, and significantly improved the arthritic condition. Taken together, the anti-arthritic effect of epalrestat was diminished or even overridden by the excessive accumulation of toxic 4-HNE or other reactive aldehydes in AIA rats due to AR inhibition. Co-treatment with NAC significantly reversed epalrestat-induced upregulation of 4-HNE level and potentiated the anti-arthritic effect of epalrestat, suggesting that the combined therapy of epalrestat with NAC may sever as a potential approach in treating RA. Importantly, it could be regarded as a safe intervention for RA patients who need epalrestat for the treatment of diabetic complications.