Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Gao, Yanan; Li, Songli; Wang, Jiaqi; Luo, Chaochao; Zhao, Shengguo; Zheng, Nan

doi:10.3390/toxins10010013

Cited by 81 publications

(65 citation statements)

References 61 publications

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“…In a similar study, CacO-2/TC7 cells exposed to AFM1 (3.2 and 33 nM) for 24 h showed reduced TEER of the monolayer and accelerated transport of the aflatoxin through it, meanwhile, the TJs and their constitutive proteins remained intact [132]. Likewise, the selective permeability of CacO-2 cells was disrupted upon exposure to different amounts of AFM1 (0.2 to 20 µM) for 48 h [133]. The latter study associated the permeability disruption to reduction of TEER, down-regulation of the expression of structural TJ proteins (claudin-3, claudin-4, occludin, zonula occludens-1), and decrease in the levels of p44/42 mitogen-activated protein kinase (MAPK) involved in cell death or cell survival.…”

Section: Innate Immunitymentioning

confidence: 75%

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Benkerroum

2020

IJERPH

354

214

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There are presently more than 18 known aflatoxins most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has been by far the most studied; yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity—which are the best known—still suffer from limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the hepatotoxic algal microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the field of the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

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Section: Innate Immunitymentioning

confidence: 75%

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Benkerroum

2020

IJERPH

354

214

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“…[29][30][31] . There are evidences proved that LPS-induced inflammation destroyed the integrity of intestinal epithelial cells and tight junctions [17] . In the present research, we determined that betaine(0-2 mmol/L) improved the expression of TJ proteins and with the concentration of 2 mmol/L, betaine was able to relive the down-regulation of TJ proteins completely which is induced by LPS.…”

Section: Discussionmentioning

confidence: 99%

“…However, this approach has been questioning due to its abnormal characters including rapid growth and proliferation properties. Recently, differentiated IPEC-J2 cell line is recognized as a better cellular model to explore the role of the intestinal barrier [17] . Thus, in this study, IPEC-J2 cells were applied as a cellular model to evaluate the effects of Bet alone or combined with LPS on intestinal barrier function.…”

Section: Introductionmentioning

confidence: 99%

Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

et al. 2019

Preprint

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Background: The intestinal epithelial barrier, which works as the first line of defense between the intestinal environment and the parasitifer, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine (Bet) has excellent anti-inflammatory activity but whether Bet has any effect on tight junction proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model, the purpose of this study is to explore the pharmacological effect of Bet on improving intestinal barrier function represented by TJ proteins.Results: The results demonstrated that Bet enhanced the expression of tight junction proteins while LPS（ 1μg /m L）downregulates the expression of these proteins. Furthermore, Bet attenuates LPS-induced decreases of tight junction proteins both shown by WB and RT-PCR. The immunofluorescent images consistently revealed that LPS induced the disruption of tight junction protein Claudin-1 and reduced its expression while Bet could reverse these alterations. Similar protective role of Bet on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that Bet attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

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“…Early studies on OTA focused mainly on the diversity of toxic effects in different animal species [17][18][19]. Recent studies, however, have reported the toxic effect of OTA on the intestine [20,21]. OTA-induced intestinal damage has been reported in both animals and in vitro intestinal models [22,23].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Yang

Gao

Yan

et al. 2019

Toxins

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Ochratoxin A (OTA), an important mycotoxin that occurs in food and animal feed, has aroused widespread concern in recent years. Previous studies have indicated that OTA causes nephrotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, cytotoxicity, and neurotoxicity. The intestinal toxicity of OTA has gradually become a focus of research, but the mechanisms underlying this toxicity have not been described. Here, differentiated Caco-2 cells were incubated for 48 h with different concentrations of OTA and transcriptome analysis was used to estimate damage to the intestinal barrier. Gene expression profiling was used to compare the characteristics of differentially expressed genes (DEGs). There were altogether 10,090 DEGs, mainly clustered into two downregulation patterns. The Search Tool for Retrieval of Interacting Genes (STRING), which was used to analyze the protein–protein interaction network, indicated that 24 key enzymes were mostly responsible for regulating cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was used to validate eight genes, three of which were key genes (CASP3, CDC25B, and EGR1). The results indicated that OTA dose-dependently induces apoptosis in differentiated Caco-2 cells. Transcriptome analysis showed that the impairment of intestinal function caused by OTA might be partly attributed to apoptosis, which is probably associated with downregulation of murine double minute 2 (MDM2) expression and upregulation of Noxa and caspase 3 (CASP3) expression. This study has highlighted the intestinal toxicity of OTA and provided a genome-wide view of biological responses, which provides a theoretical basis for enterotoxicity and should be useful in establishing a maximum residue limit for OTA.

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Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

Cited by 81 publications

References 61 publications

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action

Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

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