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Updated: Aug 17, 2025
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos
Zhengkang Su1, Kaiyu Guan2, Yunbin Liu3
1Zhejiang 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.
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.
Insights
Opicapone, a Parkinson's drug, causes developmental toxicity in zebrafish larvae. High doses are lethal, while lower doses induce developmental delays and oxidative stress, impacting embryonic development.
Area of Science:
- Developmental Toxicology
- Neuropharmacology
- Zebrafish Models
Background:
- Psychoactive drugs can threaten fetal development.
- Opicapone, a COMT inhibitor, treats Parkinson's disease and may affect other dopamine-related disorders.
- The impact of opicapone on embryonic development is unknown.
Purpose of the Study:
- To investigate the developmental toxicity of opicapone in zebrafish larvae.
- To understand the effects of opicapone on embryonic development and identify potential risks.
Main Methods:
- Zebrafish larvae were exposed to varying concentrations of opicapone.
- Developmental parameters, including body size, head size, and locomotor behavior, were assessed.
- Dopamine levels, glutathione status, and antioxidant enzyme activities were measured.
- Gene expression related to glutathione metabolism and immune response was analyzed.
Main Results:
- High opicapone concentration (30 μM) was teratogenic and lethal.
- Low opicapone concentration caused developmental delays (shortened body, smaller head, reduced movement).
- Opicapone increased dopamine levels and induced oxidative damage, indicated by altered glutathione and antioxidant enzyme activity.
- Enhanced glutathione metabolism and cytokine-cytokine receptor interaction suggest immune responses.
Conclusions:
- Opicapone exhibits significant developmental toxicity in zebrafish larvae.
- Exposure can lead to teratogenicity, lethality, developmental delays, and oxidative stress.
- These findings highlight potential risks of opicapone exposure during embryonic development.
