Tizoxanide as a novel theraputic candidate for osteoarthritis

Bowei Ni; Jiyuan Yan; Wenxiang Cai; Yifan Xiao; Chang Tu

doi:10.1016/j.heliyon.2023.e19472

Tizoxanide as a novel theraputic candidate for osteoarthritis

Heliyon. 2023 Aug 26;9(9):e19472. doi: 10.1016/j.heliyon.2023.e19472. eCollection 2023 Sep.

Authors

Bowei Ni^{1

2

3}, Jiyuan Yan^{1

2}, Wenxiang Cai¹, Yifan Xiao⁴, Chang Tu¹

Affiliations

¹ Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China.
² Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
³ Department of Orthopedics, Tongren Hospital of Wuhan University, Wuhan Third Hopspital, Wuhan, Hubei, PR China.
⁴ Department of Pathology and Pathophysiology, Medical College, Jianghan University, Wuhan, Hubei, PR China.

Abstract

Osteoarthritis (OA) is a frequently seen degenerative joint disease in the elderly. Its pathogenesis is highly related to the local inflammatory reaction and autophagy. Tizoxanide (Tiz), the main active metabolite of nitazoxanide, has proved its anti-inflammatory properties in several diseases. However, the exact role of Tiz in OA remains to explore. In this study, we investigated the anti-arthritic effects and the underlying molecular mechanisms of Tiz on rat OA. The results showed that Tiz could attenuate the IL-1β-induced inflammatory disorders, cartilage matrix damage and autophagy reduction in rat chondrocytes. Moreover, employment of autophagy inhibitor 3-methyladenine (3-MA) could antagonize the protective effects of Tiz in IL-1β-treated rat chondrocytes. Additionally, Tiz also inhibited the IL-1β-induced PI3K/AKT/mTOR and P38/JNK phosphorylation in chondrocytes. In vivo, intra-articular injection of Tiz could significantly alleviate the progression of cartilage damage in rat OA model. Briefly, our study demonstrated the therapeutic potential of Tiz in OA, suggesting that Tiz administration might serve as a promising strategy in OA therapy.

Keywords: 3-Methyladenine; Autophagy; Osteoarthritis; P38/JNK; PI3K/AKT/mTOR; Tizoxanide.