Evaluation of Tacrolimus’ Adverse Effects on Zebrafish in Larval and Adult Stages by Using Multiple Physiological and Behavioral Endpoints

Author:

Feng Wen-Wei123ORCID,Chen Hsiu-Chao123,Audira Gilbert45,Suryanto Michael Edbert45ORCID,Saputra Ferry45ORCID,Kurnia Kevin Adi45ORCID,Vasquez Ross D.67ORCID,Casuga Franelyne P.67,Lai Yu-Heng8,Hsiao Chung-Der459ORCID,Hung Chih-Hsin1

Affiliation:

1. Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan

2. Department of Dermatology, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan

3. Dr. Feng’s Dermatology Clinic, Kaohsiung 82445, Taiwan

4. Department of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan 320314, Taiwan

5. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan 320314, Taiwan

6. Research Center for Natural and Applied Sciences, Department of Pharmacy, University of Santo Tomas, Manila 1008, Philippines

7. The Graduate School, Faculty of Pharmacy, University of Santo Tomas, Manila 1008, Philippines

8. Department of Chemistry, Chinese Culture University, Taipei 11114, Taiwan

9. Research Center for Aquatic Toxicology and Pharmacology, Chung Yuan Christian University, Chung-Li, Taoyuan 320314, Taiwan

Abstract

Tacrolimus (FK506) is a common immunosuppressant that is used in organ transplantation. However, despite its importance in medical applications, it is prone to adverse side effects. While some studies have demonstrated its toxicities to humans and various animal models, very few studies have addressed this issue in aquatic organisms, especially zebrafish. Here, we assessed the adverse effects of acute and chronic exposure to tacrolimus in relatively low doses in zebrafish in both larval and adult stages, respectively. Based on the results, although tacrolimus did not cause any cardiotoxicity and respiratory toxicity toward zebrafish larvae, it affected their locomotor activity performance in light–dark locomotion tests. Meanwhile, tacrolimus was also found to slightly affect the behavior performance, shoaling formation, circadian rhythm locomotor activity, and color preference of adult zebrafish in a dose-dependent manner. In addition, alterations in the cognitive performance of the fish were also displayed by the treated fish, indicated by a loss of short-term memory. To help elucidate the toxicity mechanism of tacrolimus, molecular docking was conducted to calculate the strength of the binding interaction between tacrolimus to human FKBP12. The results showed a relatively normal binding affinity, indicating that this interaction might only partly contribute to the observed alterations. Nevertheless, the current research could help clinicians and researchers to further understand the toxicology of tacrolimus, especially to zebrafish, thus highlighting the importance of considering the toxicity of tacrolimus prior to its usage.

Publisher

MDPI AG

Reference98 articles.

1. Mariotti, A., Dowd, F.J., and Johnson, B.S. (2017). Pharmacology and Therapeutics for Dentistry, Elsevier Health Sciences. [7th ed.].

2. Cohen, J., Powderly, W.G., and Opal, S.M. (2017). Infectious Diseases, Elsevier Health Sciences. [4th ed.].

3. The impact of tacrolimus exposure on extrarenal adverse effects in adult renal transplant recipients;Campagne;Br. J. Clin. Pharmacol.,2019

4. Neuropsychologic side-effects of tacrolimus in pediatric renal transplantation;Kemper;Clin. Transplant.,2003

5. Population pharmacokinetic modelling and Bayesian estimation of tacrolimus exposure: Is this clinically useful for dosage prediction yet?;Brooks;Clin. Pharmacokinet.,2016

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3