Ticlopidine induces embryonic development toxicity and hepatotoxicity in zebrafish by upregulating the oxidative stress signaling pathway

Xu, Ran; Xu, Pengxiang; Wei, Haiyan; Huang, Yong; Zhu, Xiaodan; Lin, Cheng Chang; Yan, Zhimin; Xin, Liuyan; Li, Lin; Lv, Weiming; Zeng, Shuqin; Tian, GY; Ma, Jinze; Cheng, Bo; Lu, Huiqiang; Chen, Yi-Jian

doi:10.1016/j.ecoenv.2023.115283

Cited by 4 publications

(1 citation statement)

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“…Previously, research on HIF-1 mainly focused on its active subunit HIF-1α, which is cumulatively expressed under hypoxia conditions and is a key regulator of oxygen content balance in mammals. Research shows that the HIF-1 pathway can regulate ROS by regulating mitochondrial function and changing the degree of electron leakage in the electron transport chain, thus affecting cell survival and proliferation [ 30 , 31 , 32 ]. In addition, the MAPK signaling pathway enriched by network toxicology is also closely related to liver inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms

Sun,

Zhang,

Yin

et al. 2023

Toxics

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Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

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Section: Discussionmentioning

confidence: 99%