PUBLICATION
Evaluation of the Adverse Effects of Chronic Exposure to Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments
- Authors
- Audira, G., Ngoc Anh, N.T., Ngoc Hieu, B.T., Malhotra, N., Siregar, P., Villalobos, O., Villaflores, O.B., Ger, T.R., Huang, J.C., Chen, K.H., Hsiao, C.D.
- ID
- ZDB-PUB-201002-128
- Date
- 2020
- Source
- Biomolecules 10(9): (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- acetylcholinesterase inhibitor, behavior, dementia, donepezil, zebrafish
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Brain/drug effects*
- Brain/metabolism
- Cholinesterase Inhibitors/toxicity
- Donepezil/toxicity*
- Environmental Exposure/adverse effects*
- Locomotion/drug effects
- Locomotion/physiology
- Malondialdehyde/metabolism
- Memory, Short-Term/drug effects
- Memory, Short-Term/physiology
- Motor Activity/drug effects
- Motor Activity/physiology
- Muscles/drug effects
- Muscles/metabolism
- Muscles/physiology
- Reactive Oxygen Species/metabolism
- Superoxide Dismutase/metabolism
- Toxicity Tests, Chronic/methods*
- Zebrafish/physiology*
- PubMed
- 32962160 Full text @ Biomolecules
Citation
Audira, G., Ngoc Anh, N.T., Ngoc Hieu, B.T., Malhotra, N., Siregar, P., Villalobos, O., Villaflores, O.B., Ger, T.R., Huang, J.C., Chen, K.H., Hsiao, C.D. (2020) Evaluation of the Adverse Effects of Chronic Exposure to Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments. Biomolecules. 10(9):.
Abstract
Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping