Time dependent impact of copper oxide nanomaterials on the expression of genes associated with oxidative stress, metal binding, inflammation and mucus secretion in single and co-culture intestinal in vitro models.

Abstract

The potential for ingestion of copper oxide nanomaterials (CuO NMs) is increasing due to their increased exploitation. Investigation of changes in gene expression allows toxicity to be detected at an early stage of NM exposure and can enable investigation of the mechanism of toxicity. Here, undifferentiated Caco-2 cells, differentiated Caco-2 cells, Caco-2/HT29-MTX (mucus secreting) and Caco-2/Raji B (M cell model) co-cultures were exposed to CuO NMs and copper sulphate (CuSO4) in order to determine their impacts. Cellular responses were measured in terms of production of reactive oxygen species (ROS), the gene expression of an antioxidant (haem oxygenase 1 (HMOX1)), the pro-inflammatory cytokine (interleukin 8 (IL8)), the metal binding (metallothionein 1A and 2A (MT1A and MT2A)) and the mucus secreting (mucin 2 (MUC2)), as well as HMOX-1 protein level. While CuSO4 induced ROS production in cells, no such effect was observed for CuO NMs. However, these particles did induce an increase in the level of HMOX-1 protein and upregulation of HMOX1, MT2A, IL8 and MUC2 genes in all cell models. In conclusion, the expression of HMOX1, IL8 and MT2A were responsive to CuO NMs at 4 to 12 h post exposure when investigating the toxicity of NMs using intestinal in vitro models. These findings can inform the selection of endpoints, timepoints and models when investigating NM toxicity to the intestine in vitro in the future.

• Authors: Victor C Ude, David M Brown, Vicki Stone, Helinor J Johnston
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 74 Pg. 105161 (Aug 2021) ISSN: 1879-3177 [Electronic] England
• PMID: 33839236 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• CXCL8 protein, human
• Interleukin-8
• MT1A protein, human
• MT2A protein, human
• MUC2 protein, human
• Mucin-2
• Reactive Oxygen Species
• Copper
• Metallothionein
• HMOX1 protein, human
• Heme Oxygenase-1
• Copper Sulfate
• cupric oxide

Topics

• Cell Line
• Coculture Techniques
• Copper (toxicity)
• Copper Sulfate (toxicity)
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Humans
• Inflammation (genetics)
• Interleukin-8 (genetics)
• Intestines (drug effects)
• Metallothionein (genetics)
• Mucin-2 (genetics)
• Mucus (metabolism)
• Nanostructures (toxicity)
• Oxidative Stress (drug effects, genetics)
• Reactive Oxygen Species (metabolism)