BPA and low-Se exacerbate apoptosis and autophagy in the chicken bursa of Fabricius by regulating the ROS/AKT/FOXO1 pathway
SCIENCE OF THE TOTAL ENVIRONMENT(2024)
Abstract
Bisphenol A (BPA) is a ubiquitous environmental pollutant that can have harmful effects on human and animal immune systems by inducing oxidative stress. Selenium (Se) deficiency damages immune organ tissues and exhibits synergistic effects on the toxicity of environmental pollutants. However, oxidative stress, cell apoptosis, and autophagy caused by the combination of BPA and low -Se, have not been studied in the bursa of Fabricius of the immune organ of poultry. Therefore, in this study, BPA and/or low -Se broiler models and chicken lymphoma cells (MDCC-MSB-1 cells) models were established to investigate the effects of BPA and/or low -Se on the bursa of Fabricius of poultry. The data showed that BPA and/or low -Se disrupted the normal structure of the bursa of Fabricius, BPA (60 mu M) significantly reduced the activity of MDCC-MSB-1 cells and disrupted normal morphology (IC50 = 192.5 +/- 1.026 mu M). Compared with the Control group, apoptosis and autophagy were increased in the BPA or low -Se groups, and the generation of reactive oxygen species (ROS) was increased. This inhibited the AKT/FOXO1 pathway, leading to mitochondrial fusion/division imbalance (Mfn1, Mfn2, OPA1 were increased, DRP1 was decreased) and dysfunction (CI-NDUFB8, CII-SDHB, CIII-UQCRC2, CIV-MTCO1, CVATP5A1, ATP). Furthermore, combined exposure of BPA and low -Se aggravated the above -mentioned changes. Treatment with N-acetylcysteine (NAC) reduced ROS levels and activated the AKT/FOXO1 pathway to further alleviate BPA and low -Se -induced apoptosis and autophagy. Apoptosis induced by low -Se + BPA was exacerbated after 3-Methyladenine (3 -MA, autophagy inhibitor) treatment. Together, these results indicated that BPA and low -Se aggravated apoptosis and autophagy of the bursa of Fabricius in chickens by regulating the ROS/AKT/ FOXO1 pathway.
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Key words
AKT/FOXO1,Apoptosis,Autophagy,Bisphenol A,Low-selenium,Mitochondrial function
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