Cardiac Toxicity Induced by Long-Term Environmental Levels of MC-LR Exposure in Mice

Canqun Yan; Ying Liu; Yue Yang; Isaac Yaw Massey; Linghui Cao; Muwaffak Al Osman; Fei Yang

doi:10.3390/toxins15070427

Cardiac Toxicity Induced by Long-Term Environmental Levels of MC-LR Exposure in Mice

Toxins (Basel). 2023 Jun 30;15(7):427. doi: 10.3390/toxins15070427.

Authors

Canqun Yan¹, Ying Liu², Yue Yang³, Isaac Yaw Massey², Linghui Cao⁴, Muwaffak Al Osman³, Fei Yang^{2

3

5}

Affiliations

¹ Department of Health Management Center, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421009, China.
² Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421009, China.
³ Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410017, China.
⁴ Changsha Central Hospital, Changsha 410004, China.
⁵ Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang 421009, China.

Abstract

Cyanobacterial blooms are considered a serious global environmental problem. Recent studies provided evidence for a positive association between exposure to microcystin-LR (MC-LR) and cardiotoxicity, posing a threat to human cardiovascular health. However, there are few studies on the cardiotoxic effects and mechanisms of long-term low-dose MC-LR exposure. Therefore, this study explored the long-term toxic effects and toxic mechanisms of MC-LR on the heart and provided evidence for the induction of cardiovascular disease by MC-LR. C57BL/6 mice were exposed to 0, 1, 30, 60, 90, and 120 μg/L MC-LR via drinking water for 9 months and subsequently necropsied to examine the hearts for microstructural changes using H&E and Masson staining. The results demonstrated fibrotic changes, and qPCR and Western blots showed a significant up-regulation of the markers of myocardial fibrosis, including TGF-β1, α-SMA, COL1, and MMP9. Through the screening of signaling pathways, it was found the expression of PI3K/AKT/mTOR signaling pathway proteins was up-regulated. These data first suggested MC-LR may induce myocardial fibrosis by activating the PI3K/AKT/mTOR signaling pathway. This study explored the toxicity of microcystins to the heart and preliminarily explored the toxic mechanisms of long-term toxicity for the first time, providing a theoretical reference for preventing cardiovascular diseases caused by MC-LR.

Keywords: PI3K/AKT/mTOR signaling pathway; chronic toxicity; microcystins; myocardial fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cardiotoxicity*
Fibrosis
Humans
Mice
Mice, Inbred C57BL
Microcystins* / toxicity
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases

Substances

cyanoginosin LR
Microcystins
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the Hunan Province Excellent Youth Fund (2020JJ3053); the National Natural Science Foundation of China (81773393); the Key Research and Development Projects in Hunan Province (2019SK2041); the Natural Science Joint Fund of Hunan Province (2021JJ50096).