Peripheral neuroprotective potential and toxicological profile of fascaplysin in zebrafish models.

IF 1.4 Q3 ANATOMY & MORPHOLOGY
Ki-Hoon Park, Youngbuhm Huh, Hyung-Joo Chung, Hiroyuki Konishi, Junyang Jung, Na Young Jeong
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Abstract

Fascaplysin is a bioactive compound derived from marine sponges, which have anticancer properties and potential neuroprotective effects mediated by mitigation of oxidative stress-induced neurotoxicity. This study investigated the concentration-dependent effects of fascaplysin in zebrafish models, focusing on embryonic survival, cardiac function, melanocyte formation, and peripheral nerve health. Zebrafish embryos were exposed to fascaplysin at concentrations ranging from 10 nM to 100 μM, and developmental parameters were assessed. At higher concentrations (≥1 μM), fascaplysin significantly decreased embryo survival rates, delayed hatching, impaired cardiac function, and caused morphological abnormalities, including disruption of melanocyte formation and structural deformities. By contrast, lower concentrations (10 nM and 100 nM) did not exhibit significant toxicity. In adult zebrafish, fascaplysin at 100 nM reduced the expression of superoxide-producing enzymes and preserved peripheral nerve integrity following injury, as demonstrated by maintenance of fluorescence in transgenic zebrafish with expression of green fluorescent protein in Schwann cells. These findings suggest that fascaplysin exhibits peripheral neuroprotective effects at low concentrations, potentially through the reduction of oxidative stress and preservation of Schwann cell function. However, the toxicity observed at higher concentrations highlights the importance of dose optimization. Fascaplysin is a promising candidate for the development of new therapeutic strategies for peripheral neuropathies, and further studies are required to elucidate the underlying mechanisms and validate its efficacy in mammalian models.

fascaplysin在斑马鱼模型中的周围神经保护潜力和毒理学分析。
Fascaplysin是一种从海绵中提取的生物活性化合物,具有抗癌特性和潜在的神经保护作用,可以减轻氧化应激诱导的神经毒性。本研究研究了fascaplysin在斑马鱼模型中的浓度依赖性作用,重点关注胚胎存活、心功能、黑素细胞形成和周围神经健康。将斑马鱼胚胎暴露于10 nM至100 μM浓度的fascaplysin中,并评估其发育参数。在较高浓度(≥1 μM)下,fascaplysin显著降低胚胎存活率,延迟孵化,损害心功能,并引起形态学异常,包括黑素细胞形成中断和结构畸形。相比之下,较低浓度(10 nM和100 nM)没有表现出明显的毒性。在成年斑马鱼中,100 nM的fascaplysin降低了产生超氧化物酶的表达,并保护了损伤后周围神经的完整性,这在转基因斑马鱼的雪旺细胞中表达了绿色荧光蛋白,从而维持了荧光。这些发现表明,fascaplysin在低浓度下表现出周围神经保护作用,可能通过减少氧化应激和保存雪旺细胞功能。然而,在较高浓度下观察到的毒性突出了剂量优化的重要性。Fascaplysin是开发周围神经病变新治疗策略的有希望的候选药物,需要进一步研究阐明其潜在机制并验证其在哺乳动物模型中的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Anatomy & Cell Biology
Anatomy & Cell Biology ANATOMY & MORPHOLOGY-
CiteScore
1.80
自引率
9.10%
发文量
75
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