Abstract：
Cysteamine, a sulfhydryl compound, is an intermediate in the metabolism of coenzyme A to taurine in living organisms. However, the potential side effects of cysteamine such as hepatotoxicity in pediatric patients have been reported in some studies. To evaluate the impact of cysteamine on infants and children, larval zebrafish (a vertebrate model) were exposed to 0.18, 0.36 and 0.54 mM cysteamine from 72 hpf to 144 hpf. Alterations in general and pathological evaluation, biochemical parameters, cell proliferation, lipid metabolism factors, inflammatory factors and Wnt signaling pathway levels were examined. Increased liver area and lipid accumulation were observed in liver morphology, staining and histopathology in a dose-dependent manner with cysteamine exposure. In addition, the experimental cysteamine group exhibited higher alanine aminotransferase, aspartate aminotransferase, total triglyceride and total cholesterol levels than the control group. Meanwhile, the levels of lipogenesis-related factors ascended whereas lipid transport-related factors descended. Oxidative stress indicators such as reactive oxygen species, MDA and SOD were upregulated after cysteamine exposure. Afterwards, transcription assays revealed that biotinidase and Wnt pathway-related genes were upregulated in the exposed group, and inhibition of Wnt signaling partially rescued the abnormal liver development. The current study found that cysteamine-induced hepatotoxicity in larval zebrafish is due to inflammation and abnormal lipid metabolism, which is mediated by biotinidase (a potential pantetheinase isoenzyme) and Wnt signaling. This provides a perspective on the safety of cysteamine administration in children and identifies potential targets for protection against adverse reactions.
摘要：
半胱胺,巯基化合物，是生物体中辅酶A代谢为牛磺酸的中间体。然而,一些研究已经报道了半胱胺对儿科患者的潜在副作用,如肝毒性.评估半胱胺对婴儿和儿童的影响，幼体斑马鱼（脊椎动物模型）暴露于72hpf至144hpf的0.18、0.36和0.54mM半胱胺。一般和病理评估的改变，生化参数，细胞增殖，脂质代谢因子，检测炎症因子和Wnt信号通路水平。在肝脏形态学上观察到肝脏面积和脂质积累增加，半胱胺暴露的染色和组织病理学呈剂量依赖性。此外,实验半胱胺组表现出更高的丙氨酸氨基转移酶，天冬氨酸转氨酶,总甘油三酯和总胆固醇水平高于对照组。同时,脂肪生成相关因子水平上升，而脂质转运相关因子水平下降。氧化应激指标，如活性氧，半胱胺暴露后MDA和SOD上调。之后,转录测定显示，在暴露组中，生物素酶和Wnt通路相关基因上调，Wnt信号的抑制部分挽救了异常的肝脏发育。目前的研究发现半胱胺对幼体斑马鱼的肝毒性是由于炎症和脂质代谢异常,它是由生物素酶（一种潜在的泛肽酶同工酶）和Wnt信号介导的。这提供了儿童半胱胺给药安全性的观点，并确定了预防不良反应的潜在目标。
