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潜在抗类风湿关节炎候选药物左旋咪唑的安全性评估

Safety Evaluation of a Potential Anti-Rheumatoid Arthritis Candidate, Levamisole.

作者信息

Wang Jun-Xiang, Zhang Jia-Hui, Guo Mu, Huang Wei-Rui, Zheng Han-Lu, Liao Yi-Qi, Yan Ying-Xue, Lin Zhao-Long, Qiu Neng-Fu, Dai Cui-Ting, Yu Xiang-Bin, Yu Yue

机构信息

School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People's Republic of China.

Department of Pathology, The People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People's Republic of China.

出版信息

J Inflamm Res. 2024 Oct 29;17:7837-7849. doi: 10.2147/JIR.S477013. eCollection 2024.

Abstract

INTRODUCTION

Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM's potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.

METHODS

To evaluate the potential toxicity of LVM, a 28-day oral administration was conducted in SD rats, assessing general toxicity and neurotoxicity using serum biochemical indicators, the Morris water maze test, transmission electron microscopy, and H&E staining. Subsequently, the therapeutic effects of LVM on RA were evaluated.

RESULTS

The results showed that 30 mg/kg LVM has promising therapeutic effects in the treatment of RA with negligible toxicity from 45 mg/kg to 180 mg/kg.

DISCUSSIONS

This study provides valuable preclinical data on the safety and efficacy of LVM, laying the groundwork for future clinical applications and potentially offering a safer and more effective treatment option for RA patients.

摘要

引言

鉴于目前类风湿性关节炎(RA)治疗方法的局限性和不良反应,迫切需要更安全、有效的治疗选择。左旋咪唑(LVM)是一种非特异性免疫调节剂,具有治疗皮肤病、肿瘤和自身免疫性疾病的潜力。尽管左旋咪唑名声有争议,但鉴于其潜力,本研究旨在调查其对类风湿性关节炎的安全性和治疗效果。

方法

为评估左旋咪唑的潜在毒性,对SD大鼠进行了为期28天的口服给药,使用血清生化指标、莫里斯水迷宫试验、透射电子显微镜和苏木精-伊红染色评估一般毒性和神经毒性。随后,评估了左旋咪唑对类风湿性关节炎的治疗效果。

结果

结果表明,30mg/kg的左旋咪唑在治疗类风湿性关节炎方面具有良好的治疗效果,而45mg/kg至180mg/kg的毒性可忽略不计。

讨论

本研究提供了关于左旋咪唑安全性和有效性的宝贵临床前数据,为未来的临床应用奠定了基础,并可能为类风湿性关节炎患者提供更安全、有效的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7306/11531285/822325c4c44d/JIR-17-7837-g0001.jpg

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