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  2. Aspirin ameliorates the neurotoxicity of benzo[a]pyrene in mice and HT22 cells: Possible role of miRNA-mRNA network

Aspirin ameliorates the neurotoxicity of benzo[a]pyrene in mice and HT22 cells: Possible role of miRNA-mRNA network

  • Food Chem Toxicol. 2023 Jun 24;113919. doi: 10.1016/j.fct.2023.113919.
Jinfeng Zhang 1 Yangyang Li 1 Huan Li 1 Aixiang Liu 1 Jingjing Cao 1 Xin Li 2 Na Xia 1 Zhihong Zhang 1 Jianying Bai 1 Hongmei Zhang 3
Affiliations

Affiliations

  • 1 Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China.
  • 2 Center of Disease Control and Prevention, Taiyuan Iron and Steel Company, Taiyuan, 030003, Shanxi, China.
  • 3 Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China; Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Taiyuan, 030001, Shanxi, China; Key Laboratory of Cellular Physiology, Taiyuan, 030001, Shanxi, China; Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: hm.zhang@sxmu.edu.cn.
Abstract

Benzo[a]pyrene (B[a]P) is neurotoxic, however, the mechanism and potential prevention are yet not clear. This study explored the miRNA-mRNA network in the B[a]P-induced neurotoxicity in mice and HT22 cells and the intervention of aspirin (ASP). HT22 cells were treated for 48 h with DMSO, B[a]P (20 μM), or both B[a]P (20 μM) and ASP (4 μM). Following B[a]P treatment, compared to the DMSO controls, HT22 cells showed injured cell morphology, reduced cell viability and neurotrophic factor concentrations, and increased LDH leakage, Aβ1-42, and inflammatory factor concentrations, which were improved by ASP. RNA Sequencing and qPCR verified the significant differences of miRNA and mRNA profiles following B[a]P treatment, which were rescued by ASP. Bioinformatics analysis suggested the miRNA-mRNA network could be involved in the neurotoxicity of B[a]P and the intervention of ASP. The neurotoxicity and neuroinflammation were induced in mice's brains by B[a]P, and the target miRNA and mRNA were proved to be consistent with in vitro, which were ameliorated by ASP. The findings demonstrate a possible role of miRNA-mRNA network in the B[a]P-induced neurotoxicity. If this is confirmed by additional experiments, it will provide a promising pathway of intervention against B[a]P, using ASP or other agents with fewer toxic effects.

Keywords

Aspirin; Benzo[a]pyrene; Ectonucleoside triphosphate diphosphohydrolase 4; Neurotoxicity; miRNA-mRNA network.

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