Long-Term Exposure to Microcystin-LR Induces Gastric Toxicity by Activating the Mitogen-Activated Protein Kinase Signaling Pathway

Ying Liu; Yafang Li; Qinmei Tan; Yilin Lv; Yan Tang; Yue Yang; Xueqiong Yao; Fei Yang

doi:10.3390/toxins15090574

Long-Term Exposure to Microcystin-LR Induces Gastric Toxicity by Activating the Mitogen-Activated Protein Kinase Signaling Pathway

Toxins (Basel). 2023 Sep 18;15(9):574. doi: 10.3390/toxins15090574.

Authors

Ying Liu¹, Yafang Li¹, Qinmei Tan¹, Yilin Lv¹, Yan Tang¹, Yue Yang², Xueqiong Yao¹, Fei Yang^{1

2

3}

Affiliations

¹ 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.
² The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421009, China.
³ 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

Previous studies have primarily concentrated on the hepatotoxicity of MC-LR, whereas its gastric toxicity effects and mechanisms of long-term exposure under low dosage remain unknown. Herein, the gastric tissue from C57BL/6 mice fed with drinking water contaminated by low-dose MC-LR (including 1, 60, and 120 μg/L) was investigated. The results obtained showed that exposure to different concentrations of MC-LR resulted in significant shedding and necrosis of gastric epithelial cells in mice, and a down-regulation of tight junction markers, including ZO-1, Claudin1, and Occludin in the stomach, which might lead to increased permeability of the gastric mucosa. Moreover, the protein expression levels of p-RAF/RAF, p-ERK1/2/ERK1/2, Pink1, Parkin, and LC3-II/LC-3-I were increased in the gastric tissue of mice exposed to 120 μg/L of MC-LR, while the protein expression level of P62 was significantly decreased. Furthermore, we found that pro-inflammatory factors, including IL-6 and TNF-ɑ, were dramatically increased, while the anti-inflammatory factor IL-10 was significantly decreased in the gastric tissue of MC-LR-exposed mice. The activation of the MAPK signaling pathway and mitophagy might contribute to the development of gastric damage by promoting inflammation. We first reported that long-term exposure to MC-LR induced gastric toxicity by activating the MAPK signaling pathway, providing a new insight into the gastric toxic mechanisms caused by MC-LR.

Keywords: MAPK signaling pathway; MC-LR; gastric toxicity; inflammation; mitophagy.

Publication types

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

MeSH terms

Animals
Factor X
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases*
Signal Transduction*
Stomach

Substances

Mitogen-Activated Protein Kinases
cyanoginosin LR
Factor X

Grants and funding

This research was funded by the Key Research and Development Projects in Hunan Province (2022SK2089, 2019SK2041), the Huxiang Youth Talent Program (2021RC3107), the Research Foundation of Education Bureau of Hunan Province, China (22A0300), the Natural Science Foundation of Hunan Province (2023JJ40569), National College Students’ innovation and entrepreneurship training program, China, (202110555010). We thank Figdraw (www.figdraw.com (accessed on 11 June 2023)) for expert assistance in the pattern drawing.