2. Academic Validation
  3. Environmentally realistic dose of tire-derived metabolite 6PPD-Q exposure causes intestinal jejunum and ileum damage in mice via cannabinoid receptor-activated inflammation

Environmentally realistic dose of tire-derived metabolite 6PPD-Q exposure causes intestinal jejunum and ileum damage in mice via cannabinoid receptor-activated inflammation

  • Sci Total Environ. 2024 Mar 25:918:170679. doi: 10.1016/j.scitotenv.2024.170679.
Yan Yang 1,  Nan Sun 2,  Jia Lv 3,  Haojia Chen 1,  Hongqian Wang 4,  Jingjing Xu 2,  Jiayue Hu 5,  Lin Tao 2,  Mingliang Fang 6,  Yichao Huang 7
Affiliations

Affiliations

  • 1 School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China; Synergy Innovation Institute of GDUT, Shantou 515041, Guangdong, China.
  • 2 Department of Toxicology, School of Public Health, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, China.
  • 3 Department of Toxicology, School of Public Health, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, China. Electronic address: lvjia150313@163.com.
  • 4 Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 5 Department of Hygiene Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, China.
  • 6 Department of Environmental Science and Engineering, Fudan University, Shanghai, China.
  • 7 Department of Toxicology, School of Public Health, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, MOE Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, China. Electronic address: yichao.huang@ahmu.edu.cn.
PMID: 38325485 DOI: 10.1016/j.scitotenv.2024.170679
Abstract

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is a quinone derivative of a common tire additive 6PPD, whose occurrence has been widely reported both in the environment and human bodies including in adults, pregnant women and children. Yet, knowledge on the potential intestinal toxicity of 6PPD-Q in mammals at environmentally relevant dose remain unknown. In this study, the effects of 6PPD-Q on the intestines of adult ICR mice were evaluated by orally administering environmentally relevant dose or lower levels of 6PPD-Q (0.1, 1, 10, and 100 μg/kg) for 21 days. We found that 6PPD-Q disrupted the integrity of the intestinal barrier, mostly in the jejunum and ileum, but not in the duodenum or colon, in a dose-dependent manner. Moreover, intestinal inflammation manifested with elevated levels of TNF-α, IL-1, and IL-6 mostly observed in doses at 10 and 100 μg/kg. Using reverse target screening technology combining molecular dynamic simulation modeling we identified key cannabinoid receptors including CNR2 activation to be potentially mediating the intestinal inflammation induced by 6PPD-Q. In summary, this study provides novel insights into the toxic effects of emerging contaminant 6PPD-Q on mammalian intestines and that the chemical may be a Cannabinoid Receptor agonist to modulate inflammation.

Keywords

6PPD-Q; CD-1 mouse; Inflammation; Intestinal toxicity; Molecular docking.

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