The therapeutic efficacy of post-symptom 3,4-diaminopyridine treatment in cosmetic injection-induced botulism using a novel animal model

Ping He , Rongshuai Yan , Jie Liu , Pan You , Jianghe Zhang , Jinqing Li , Yiming Zhang
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Abstract

In recent years, the incidence of cosmetic injection-induced botulism has remarkably increased due to the frequent usage of botulinum neurotoxin type A (BoNT/A). To mimic and investigate this new clinical type of botulism, we established a novel animal model and evaluated the therapeutic potential of a new drug. Firstly, we injected BoNT/A into the gastrocnemius of rats to induce partial paralysis of the remaining limbs. Then, the intoxicated rats were treated with 3,4-diaminopyridine (3,4-DAP) at different stages of the disease and the forelimbs grasping strength (FGS) was evaluated. We showed that, at the sublethal dose, the FGS began to decrease at 6.00 ​± ​1.86 ​h after injection in rats, from 2.28 ​± ​0.19 ​N to 1.51 ​± ​0.18 ​N, while the FGS declined appeared earlier (4.29 ​± ​0.42 ​h) at the lethal dose, from 2.30 ​± ​0.20 ​N to 1.20 ​± ​0.16 ​N. Treatment with 3,4-DAP respectively at the time of the symptoms onset or 7 days after injection both can temporarily reverse the symptoms of muscle paralysis, indicating that 3,4-DAP may be an effective approach to relieve botulism. Overall, this study provides an available rat model and a promising therapeutic strategy for cosmetic injection-induced botulism.

利用新型动物模型研究症状后 3,4-二氨基吡啶治疗美容注射引起的肉毒中毒的疗效
近年来,由于A型肉毒杆菌神经毒素(BoNT/A)的频繁使用,美容注射诱发肉毒中毒的发病率显著上升。为了模拟和研究这种新型肉毒中毒临床类型,我们建立了一种新型动物模型,并评估了一种新药的治疗潜力。首先,我们向大鼠的腓肠肌注射 BoNT/A,诱导其余肢体部分瘫痪。然后,在疾病的不同阶段用 3,4-二氨基吡啶(3,4-DAP)治疗中毒大鼠,并评估其前肢抓握力量(FGS)。我们发现,在亚致死剂量下,大鼠的 FGS 在注射后 6.00 ± 1.86 h 开始下降,从 2.28 ± 0.19 N 降至 1.51 ± 0.18 N,而在致死剂量下,FGS 下降的时间更早(4.29 ± 0.42 h),从 2.30 ± 0.20 N 降至 1.20 ± 0.16 N。在症状出现时或注射后7天分别使用3,4-DAP治疗均可暂时逆转肌肉麻痹症状,表明3,4-DAP可能是缓解肉毒中毒的有效方法。总之,这项研究为化妆品注射引起的肉毒中毒提供了一个可用的大鼠模型和一种有前景的治疗策略。
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CiteScore
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