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Evaluation of Tacrolimus' Adverse Effects on Zebrafish in Larval and Adult Stages by Using Multiple Physiological and
Wen-Wei Feng1,2,3, Hsiu-Chao Chen1,2,3, Gilbert Audira4,5
1Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan.
Biology
|February 23, 2024
Summary
Tacrolimus (FK506) exposure in zebrafish caused behavioral and cognitive impairments, including reduced locomotor activity and short-term memory loss. These findings highlight potential aquatic toxicity of this common immunosuppressant.
Area of Science:
- Environmental Toxicology
- Aquatic Toxicology
- Pharmacology
Background:
- Tacrolimus (FK506) is a vital immunosuppressant in organ transplantation.
- Its known toxicities in mammals contrast with limited data in aquatic organisms.
- Zebrafish are increasingly used as models for environmental toxicity studies.
Purpose of the Study:
- To investigate the adverse effects of tacrolimus exposure on zebrafish.
- To assess both acute and chronic toxicity in larval and adult stages.
- To explore potential mechanisms underlying tacrolimus-induced toxicity.
Main Methods:
- Exposure of zebrafish larvae and adults to varying doses of tacrolimus.
- Behavioral assessments including locomotor activity, shoaling, and circadian rhythm.
- Cognitive function tests evaluating short-term memory.
- Molecular docking to assess tacrolimus binding to human FKBP12.
Main Results:
- Tacrolimus did not induce cardiotoxicity or respiratory toxicity in zebrafish larvae.
- Larval zebrafish exhibited impaired locomotor activity.
- Adult zebrafish showed dose-dependent alterations in behavior, shoaling, circadian rhythm, and color preference.
- Cognitive impairment, specifically short-term memory loss, was observed in treated adult fish.
- Molecular docking indicated normal binding affinity to human FKBP12, suggesting limited contribution to observed effects.
Conclusions:
- Tacrolimus exposure can induce significant behavioral and cognitive deficits in zebrafish.
- These findings underscore the need to consider tacrolimus's aquatic toxicity.
- Further research is needed to fully elucidate the toxicity mechanisms in aquatic models.
