Bisphenol A aggravates renal apoptosis and necroptosis in selenium‐deficient chickens via oxidative stress and PI3K/AKT pathway

Abstract

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.

Selenium deficiency aggravates bisphenol A‐induced autophagy in chicken kidney through regulation of nitric oxide and adenosine monophosphate activated protein kinase/mammalian target of rapamycin signaling pathway

“…Chicken embryo kidney (CEK) cells were isolated from 18‐days‐old SPF chicken embryos (Harbin Veterinary Research Institute, CAAS) based on standard techniques 26 and CEK cells were cultured in M199 medium (Gibco, Grand Island, NY) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, MA) and 1% penicillin–streptomycin (Solarbio, Beijing, China) at 37°C with 5% CO 2 in a cell incubator. BPA (Sigma‐Aldrich, Saint Louis, MO) was dissolved in anhydrous ethanol (Solarbio, Beijing, China) for a concentration of 0.01 g/ml for in vivo analysis, and BPA was dissolved in DMSO (1000 μM, Solarbio, Beijing, China), and then diluted with M199 (150.0 nM) for in vitro analysis according to our previous study 27 . Na 2 SeO 3 with analytical reagent grade (Sigma‐Aldrich, Saint Louis, MO) was dissolved in M199 medium for a preparation concentration of 1000 nM in vitro studies, and Na 2 SeO 3 was dissolved in normal saline medium for a preparation concentration of 0.03 g/ml in vivo studies.…”

“…BPA (Sigma-Aldrich, Saint Louis, MO) was dissolved in anhydrous ethanol (Solarbio, Beijing, China) for a concentration of 0.01 g/ml for in vivo analysis, and BPA was dissolved in DMSO (1000 μM, Solarbio, Beijing, China), and then diluted with M199 (150.0 nM) for in vitro analysis according to our previous study. 27 Na 2 SeO 3 with analytical reagent grade (Sigma-Aldrich, Saint Louis, MO) was dissolved in M199 medium for a preparation concentration of 1000 nM in vitro studies, and Na 2 SeO 3 was dissolved in normal saline medium for a preparation concentration of 0.03 g/ml in vivo studies. AMPK, mTOR, p62, Beclin 1, and LC3 polyclonal antibodies were purchased from the Wanlei (Shenyang, China) or Abcam (London, England), β-actin monoclonal antibody and horseradish peroxidase (HRP)-labeled secondary antibodies were provided by Sigma (Sigma-Aldrich, Saint Louis, MO).…”

The Relationship between Typical Environmental Endocrine Disruptors and Kidney Disease

“…BPA also activated the AMPK/mTOR (The 5′-adenosine monophosphate-activated protein kinase and mammalian target of rapamycin) signaling pathway, which triggers P62/Lc3/Beclin1 signaling, leading to the formation of autophagosomes and autolysosomes, and ultimately, stimulating autophagy in renal cells [ 166 , 167 ]. BPA exposure down-regulated the expression of PI3K (phosphatidylinositide 3-kinases) and AKT (protein kinase B) and activated the Bcl/Bax-Caspase 9-Caspase 3 (B-cell lymphoma/BCL2-Associated X-Caspase 9-Caspase 3) signaling pathways, leading to apoptosis and necrosis of renal cells [ 168 ]. Recent studies have shown that BPA-induced renal dysfunction was associated with ferriosis, which depends on ferritin phagocytosis, through the activation of AMPK-mTOR-ULK1 (Unc-51-like kinase 1) axis [ 169 ].…”

New Insights into How Melatonin Ameliorates Bisphenol A-Induced Colon Damage: Inhibition of NADPH Oxidase

“…Oral exposure to BPA caused severe intestinal injury, inhibited intestinal epithelial cell proliferation, promoted apoptosis, and disrupted the intestinal barrier function in mice . Additionally, research on the toxicological mechanism of BPA revealed that BPA exerted nephrotoxicity by inducing oxidative stress to promote apoptosis and necroptosis of chicken kidney cells . Exposure of bighead carp to BPA can cause DNA damage in isolated blood lymphocytes, brain, gills, liver, and kidney cells .…”

“…8 Additionally, research on the toxicological mechanism of BPA revealed that BPA exerted nephrotoxicity by inducing oxidative stress to promote apoptosis and necroptosis of chicken kidney cells. 9 Exposure of bighead carp to BPA can cause DNA damage in isolated blood lymphocytes, brain, gills, liver, and kidney cells. 10 BPA also activated the ataxia telangiectasia mutated (ATM)-p53 signaling pathway, leading to cell cycle arrest in human fetal lung fibroblasts, affecting fetal lung development and maturation.…”