Abstract
Ochratoxin A (OTA) is a widespread environmental toxin that poses a serious threat to human and animal health. OTA has been shown to cause cellular and tissue damage and is a global public health problem. However, the effects of OTA on gastrointestinal aging have not been reported. The aim of this study was to investigate the effects of OTA on intestinal aging in vitro and in vivo. In vitro experiments showed that OTA induced cellular inflammation through calcium overload and oxidative stress, significantly up-regulated the expression of P16, P21, and P53 proteins, markedly increased senescence-associated β-galactosidase activity (SA-β-gal) positive cells, and obviously decreased the expression of proliferating cell nuclear antigen (PCNA) proteins, which led to intestinal cell senescence. Meanwhile, we found that treatment with β-carotene ameliorated OTA-induced intestinal cell senescence. Consistent with the results of the in vitro experiments, in vivo studies showed that the intestinal aging of mice fed OTA was significantly higher than that of the control group. In conclusion, OTA may induce intestinal aging through calcium overload, oxidative stress and inflammation. This study lays a foundation for further research on the toxicological effects of OTA.
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This work was supported by the National Natural Science Foundation of China under Grant/Award No. 31672511.
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Guoxia Wang: conceptualization, methodology, software, validation, investigation, data curation writing—original draft, and visualization; Shuai Zhang: data curation, writing—original draft, writing—review and editing; Hainan Lan: validation, writing—review and editing; and Xin Zheng: visualization, supervision, project administration, and funding acquisition.
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Wang, G., Zhang, S., Lan, H. et al. Ochratoxin A (OTA) causes intestinal aging damage through the NLRP3 signaling pathway mediated by calcium overload and oxidative stress. Environ Sci Pollut Res 31, 27864–27882 (2024). https://doi.org/10.1007/s11356-024-32696-1
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DOI: https://doi.org/10.1007/s11356-024-32696-1