在斑马鱼胚胎中生物启发的短抗微生物的器官特异性安全概况
Sahar Isa Da'as1,2, Hajira Afreen3, Aseela Fathima4
1Research Department, Sidra Medicine, Doha, Qatar.
Frontiers in pharmacology
|June 11, 2025
概括
生物启发的短抗微生物 (BSAMPs) 在癌症治疗方面表现有前途. 然而,C和E在斑马鱼中表现出明显的器官特异性毒性,需要仔细的临床前安全评估.
科学领域:
- 生物化学和免疫学
- 药物发现和开发 药物发现和开发
- 毒理学 毒理学 毒理学
背景情况:
- 抗微生物 (AMP) 对于天生的免疫力至关重要,具有抗菌和免疫调节功能.
- 生物启发的短抗微生物 (BSAMP) 是通过计算设计的,在体外显示对结直肠癌细胞有选择性的抗癌活性.
- 需要进一步调查,以评估这些BSAMPs的体内安全性和毒性.
研究的目的:
- 在斑马鱼模型中评估两种BSAMPs,C和E的器官特异性安全性和毒性.
- 确定致命度50 (LC50) 并确定潜在的心脏毒性,神经毒性和肝毒性影响.
- 为治疗开发提供BSAMPs临床前安全概况的见解.
主要方法:
- 斑马鱼胚胎暴露于不同度的酸C和酸E.
- 评估了表型毒性,包括LC50的确定,心脏毒性,神经毒性和肝毒性.
- 观察和记录了器官特异性的影响.
主要成果:
- C的LC50值为162.2微克/毫升,E的LC50值为131.82微克/毫升.
- C在150μg/mL以下显示出最小的心血管影响,但在100μg/mL以上引起神经毒性和肝毒性.
- E会导致发育性毒性,心脏毒性 (心率降低,运动变化) 和100μg/ml以上的肝毒性.
结论:
- C和E在体内表现出不同的器官特异性毒性概况.
- 斑马鱼模型对于评估BSAMP的安全性和识别潜在的毒性非常有价值.
- 仔细的临床前评估对于BSAMPs的治疗开发至关重要.
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