2. Academic Validation
  3. Toxicology evaluation of overdose hydroxychloroquine on zebrafish (Danio rerio) embryos

Toxicology evaluation of overdose hydroxychloroquine on zebrafish (Danio rerio) embryos

  • Sci Rep. 2022 Oct 29;12(1):18259. doi: 10.1038/s41598-022-23187-9.
Min Luo # 1,  Dan Xie # 1,  Ziyuan Lin 2,  Huaqin Sun 3,  Yanyan Liu 4
Affiliations

Affiliations

  • 1 Prenatal Diagnosis Center, Department of Obstetrics & Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
  • 2 SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
  • 3 SCU-CUHK Joint Laboratory for Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. sunhuaqin@scu.edu.cn.
  • 4 Prenatal Diagnosis Center, Department of Obstetrics & Gynecologic, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. liuyy39@qq.com.
  • # Contributed equally.
PMID: 36309536 DOI: 10.1038/s41598-022-23187-9
Abstract

Potential risks of treatment with hydroxychloroquine (HCQ) include QT interval prolongation, hypoglycemia, a wide range of neuropsychiatric manifestations, hematotoxicity, and potential genetic defects. HCQ is extremely toxic when used in overdose and can lead to tachycardia, hypotension, known central nervous system, transmission defects, hypokalemia and other manifestations in individuals. The mechanism of excessive HCQ leading to these manifestations is still unclear. In this paper, overdose HCQ at different concentrations was used to treat zebrafish embryos, and the phenomena like human beings were obtained, such as increased heart rate and nervous system inhibition. With the increase of concentration to 100 μM, embryo mortality and malformation rate increased and hatching rate decreased, in situ hybridization showed abnormal differentiation of embryo germ layers and formation of vital organs. We selected embryos treated with 50 μM HCQ, in which concentration the mortality rate, hatching rate and malformation rate of the embryos were like those of the control group, for transcriptome analysis. Although the above indexes did not change significantly, the molecular changes related to the development of the heart, eye, nerve and other important organs were significant. This study provides useful information for further research on the toxicity mechanism of HCQ overdose, and provides some insight that can guide future studies in humans.

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