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

Abstract

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.

Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles

“…Kidneys play an important role in selenium homeostasis [ 41 , 52 ]. Selenium is often used as a protector against nephrotoxic effects of chemicals (e.g., [ 53 , 54 , 55 , 56 , 57 ]). However, it has been shown that rising doses of Se NPs have an increasingly pronounced nephrotoxic effect and accumulate in renal tissues [ 58 ].…”

The Relationship between Typical Environmental Endocrine Disruptors and Kidney Disease

“…BPA exposure activated autophagy-related proteins ( ATG5 , ATG7 and MAP1LC3B/LC3B ) and decreased the expression of NRF-2 and HO-1 proteins [ 162 , 163 , 164 , 165 ]. 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 ].…”