2. Academic Validation
  3. Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos

Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos

  • Ecotoxicol Environ Saf. 2022 Dec 9;249:114340. doi: 10.1016/j.ecoenv.2022.114340.
Zhengkang Su 1,  Kaiyu Guan 2,  Yunbin Liu 3,  Hai Zhang 4,  Zhengwei Huang 1,  Miaomiao Zheng 1,  Ya Zhu 1,  He Zhang 4,  Weihong Song 5,  Xi Li 6
Affiliations

Affiliations

  • 1 Zhejiang Clinical Research Center for Mental Disorders, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, School of Mental Health and The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
  • 2 Wenzhou Seventh People's Hospital, Wenzhou, Zhejiang, 325000, China.
  • 3 Yangtze River Basin Ecological Environment Monitoring and Scientific Research Center, Yangtze River Basin Ecological Environment Supervision and Administration Bureau, Ministry of Ecological Environment, Wuhan 430010, PR China.
  • 4 Zhejiang Provincial Key Lab for Subtropical Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, PR China.
  • 5 Zhejiang Clinical Research Center for Mental Disorders, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, School of Mental Health and The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, PR China. Electronic address: [email protected].
  • 6 Zhejiang Clinical Research Center for Mental Disorders, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, School of Mental Health and The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, PR China. Electronic address: [email protected].
PMID: 36508804 DOI: 10.1016/j.ecoenv.2022.114340
Abstract

The use of clinical psychoactive drugs often poses unpredictable threats to fetal development. Catechol-O-methyltransferase (COMT) is a key Enzyme that regulates dopamine metabolism and a promising target for modulation of cognitive functions. Opicapone, a newly effective third-generation peripheral COMT Inhibitor, is used for the treatment of Parkinson's disease (PD) and possibly to improve other dopamine-related disorders such as alcohol use disorder (AUD) and obsessive-compulsive disorder (OCD). The widespread use of opicapone will inevitably lead to biological exposure and damage to the human body, such as affecting fetal development. However, the effect of opicapone on embryonic development remains unknown. Here, zebrafish larvae were used as an animal model and demonstrated that a high concentration (30 μM) of opicapone exposure was teratogenic and lethal, while a low concentration also caused developmental delay such as a shortened body size, a smaller head, and reduced locomotor behaviors in zebrafish larvae. Meanwhile, opicapone treatment specifically increased the level of dopamine (DA) in zebrafish larvae. The depletion response of the total glutathione level (including oxidized and reduced forms of glutathione) and changed antioxidant enzymes activities in zebrafish larvae suggest oxidative damage caused by opicapone. In addition, enhanced glutathione metabolism and cytokine-cytokine receptor interaction were found in zebrafish larvae treated with opicapone, indicating that opicapone treatment caused an oxidation process and immune responses. Our results provide a new insight into the significant developmental toxicity of opicapone in zebrafish larvae.

Keywords

COMT inhibitor; Dopamine metabolism; Opicapone; Zebrafish larvae.

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