Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3-kinase/ threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increased reactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx, and superoxide dismutase, downregulated PI3K and AKT expressions, activated Bcl/Bax-Caspase 9-Caspase 3, and receptor-interacting protein kinase 1/mixed lineage kinase domain-like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA-exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Sedeficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.

Bisphenol A (BPA), a phenolic compound, is harmful to humans and animals as its residue in the water threatens multiple organs, especially the kidney. Low selenium (Se) diets are consumed in many regions of the world, and poor Se status has exacerbating effect on toxicity of several environmental chemicals. Here, we described the discovery path of Se deficiency aggravation on autophagy in BPA treated chicken kidney through regulating nitric oxide (NO) and adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathways.The actual dietary Se intake for chickens was 0.30 mg/kg in control group and 0.03 mg/kg in Low-Se group, and BPA exposure concentration for chickens was 0.05 g/kg. Chicken embryo kidney (CEK) cells were used in vitro and the BPA exposure concentration for CEK cells was 150 nM. We found that BPA significantly increased levels of NO and inducible nitric oxide synthase, activated AMPK/mTOR signaling pathways, thereby triggering p62/LC3/Beclin1 signaling, resulting in formations of autophagosome and autolysosome, and finally stimulating autophagy in the chicken kidney. Additionally, Se deficiency promoted the occurrence of autophagy in BPA-treated kidneys. Altogether, our findings showed that Se deficiency exacerbates BPA-induced renal autophagy in chickens via regulation of NO and AMPK/mTOR signaling pathways. These findings will improve our understandings of the mechanisms of nephrotoxicity of BPA and detoxification by Se in chickens. In addition, further work is required to determine if Se status of exposed populations needs to be considered in future epidemiological assessments.

Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.