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Pathophysiological impacts of 5-MeO-MiPT on zebrafish (Danio rerio) via the Gαq/11-PLCß signaling pathway.
Zhao, Sen; Liu, Meng; Chen, Jinyuan; Meng, Liang; Wang, Yanjiao.
Afiliación
  • Zhao S; Zhejiang Police College, Zhejiang Key Laboratory of Drug Prevention and Control Technology, Hangzhou 310053, PR China.
  • Liu M; Zhejiang Police College, Zhejiang Key Laboratory of Drug Prevention and Control Technology, Hangzhou 310053, PR China.
  • Chen J; College of Environment, Zhejiang University of Technology, Hangzhou 310014, PR China.
  • Meng L; Department of Forensic Science, Fujian Police College, Fuzhou 350007, PR China. Electronic address: mengliang@fjpsc.edu.cn.
  • Wang Y; Inovia Materials (HangZhou) Co. Ltd, Hangzhou, Zhejiang 310053, PR China. Electronic address: wangyanjiao@zju.edu.cn.
Ecotoxicol Environ Saf ; 283: 116969, 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-39216220
ABSTRACT
Novel Psychoactive Substances (NPS) derived from tryptamines has been detected in aquatic environments, leading to environmental toxicology concerns. However, the specific toxicological mechanism, underlying these NPS, remains unclear. In our previous work, we used 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) as the representative drug for NPS, and found that, 5-MeO-MiPT led to obvious behavioral inhibition and oxidative stress responses in zebrafishes model. In this study, Zebrafish were injected with varying concentrations of 5-MeO-MiPT for 30 days. RNA-seq, qPCR, metabolomics, and histopathological analyses were conducted to assess gene expression and tissue integrity. This study confirms that 5-MeO-MiPT substantially influences the transcription and expression of 13 selected genes, including ucp1, pet100, grik3, and grik4, mediated by the Gαq/11-PLCß signaling pathway. We elucidate the molecular mechanism that 5-MeO-MiPT can inhibit DAG-Ca2+/Pkc/Erk, Pkc/Pla2/PLCs and Ca2+/Camk Ⅱ/NMDA, while enhance Ca2+/Creb. Those secondary signaling pathways may be the mechanisms mediating 5-MeO-MiPT inhibiting normal behavior in zebrafish. These findings offer novel insights into the toxicological effects and addiction mechanisms of 5-MeO-MiPT. Moreover, it presents promising avenues for investigating other tryptamine-based NPS and offers a new direction for diagnosing and treating liver-brain pathway-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Transducción de Señal / Triptaminas Límite: Animals Idioma: En Revista: Ecotoxicol Environ Saf Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Transducción de Señal / Triptaminas Límite: Animals Idioma: En Revista: Ecotoxicol Environ Saf Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos