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靶向肾上腺素能受体的药物对斑马鱼早期生命阶段影响的比较研究

Comparative Study of the Effects of Drugs Targeting Adrenergic Receptors on the Early Life Stages of Zebrafish.

作者信息

Lv Junsheng, Sun Fengzhu, Li Zaitian, Qin Yueyun, Sheng Ruozhu, Sun Liwei

机构信息

College of Environment, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310032, China.

出版信息

Toxics. 2024 Aug 10;12(8):583. doi: 10.3390/toxics12080583.

Abstract

Owing to the presence of drugs targeting adrenergic receptors in aquatic ecosystems, considerable attention has been directed towards their environmental distribution and fate in recent decades. However, their potential impacts on non-target aquatic organisms, particularly fish, have received relatively limited investigation. In this study, moxisylyte (MOX) and propranolol (PRO) were selected as representatives of α- or β-adrenergic receptor antagonist, respectively, and we assessed their effects on the early life stages of zebrafish, especially on the nervous and cardiovascular systems. Although both compounds exhibited marginal effects on zebrafish survival, hatching and gross abnormality following exposure to concentrations ranging from 1 to 625 μg/L, they adversely affected the development of cardiovascular and nervous systems, but through different mechanisms of action, as evidenced by variations in gene transcriptional responses and enzyme activities. Notably, cardiovascular responses appear promising for use as potential biomarkers for exposure to drugs targeting adrenergic receptors. This study enhances our understanding of the ecotoxicological risks posed by α- and β-blockers in fish. Nonetheless, further investigation is needed to elucidate the precise mechanisms underlying the impacts of drugs targeting adrenergic receptors due to our limited knowledge of the physiological functions of the adrenergic system in fish.

摘要

由于水生生态系统中存在针对肾上腺素能受体的药物,近几十年来,人们对其在环境中的分布和归宿给予了相当多的关注。然而,它们对非靶标水生生物,特别是鱼类的潜在影响,受到的研究相对有限。在本研究中,分别选择莫西赛利(MOX)和普萘洛尔(PRO)作为α-或β-肾上腺素能受体拮抗剂的代表,我们评估了它们对斑马鱼早期生命阶段的影响,特别是对神经和心血管系统的影响。尽管在暴露于1至625μg/L的浓度后,这两种化合物对斑马鱼的存活、孵化和总体异常表现出轻微影响,但它们对心血管和神经系统的发育产生了不利影响,但作用机制不同,基因转录反应和酶活性的变化证明了这一点。值得注意的是,心血管反应有望作为暴露于针对肾上腺素能受体药物的潜在生物标志物。本研究增进了我们对鱼类中α-和β-阻滞剂所带来的生态毒理学风险的理解。尽管如此,由于我们对鱼类肾上腺素能系统的生理功能了解有限,仍需要进一步研究以阐明针对肾上腺素能受体药物影响的精确机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4462/11359397/d5b3df372337/toxics-12-00583-g001.jpg

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