Assessment of intestinal injury of hexavalent chromium using a modified in vitro gastrointestinal digestion model

Ziwei Wang, Hui Peng, Rui Zhang, Xinhang Jiang, Shen Chen, Ping Guo, Yongmei Xiao, Xiaowen Zeng, Qing Wang, Michael Aschner, Wei chun Chou, Daochuan Li, Wen Chen, Liping Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Intestinal injury assessment of hexavalent chromium (Cr-VI) in humans is crucial for quantifying assessment of adverse health risk posed by the intake of Cr (VI)-contaminated water. To overcome the deficiency in simulating human gastric reduction and intestinal absorption, we modified the constituents of simulated gastric fluid in in vitro digestion method by adding reductants glutathione (18 μM) and ascorbic acid (180 μM), which incorporated with human intestinal epithelial model to construct an in vitro gastrointestinal digestion (IVGD) model for intestinal injury assessment. Cr-VI bioaccessibility results from IVGD model showed that weak gastric acidity significantly increased the intestinal accessible Cr-VI dose by 22.41–38.43 folds. The time-course intestinal absorption indicated prolongation of intestinal exposure destroyed the intestinal epithelium, and 24 h after Cr-VI treatment was a good time point to perform intestinal absorption and toxicity assessment. A series of cell-based bioassays provided initial warning of adverse effect, suggesting that epithelial integrity exhibited greatest sensitivity to Cr-VI exposure and might be used as a sensitive marker for the toxicity assessment of oral exposure to Cr-VI. Notably, this study provides a feasible strategy for delineation of Cr-VI biotransformation and intestinal injury following ingestion exposure, which contributes to address the toxicity data gap of low-dose exposure in humans and puts forward a reference for intestinal toxicity assessment of other chemicals.

Original languageEnglish (US)
Article number115880
JournalToxicology and Applied Pharmacology
Volume436
DOIs
StatePublished - Feb 1 2022

Keywords

  • Hexavalent chromium
  • In vitro gastrointestinal digestion model
  • Intestinal injury
  • Oral exposure

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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