4.7 Article

Bisphenol A impairs renal function by reducing Na plus /K plus -ATPase and F-actin expression, kidney tubule formation in vitro and in vivo

Journal

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 246, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.114141

Keywords

Bisphenol A; Tubule formation; Oxidative stress; Na plus; K plus -ATPase; Endocrine disruptor; Renal proximal tubular epithelial cell

Funding

  1. Korean Health Tech-nology R&D Project, Ministry of Health Welfare
  2. Korea Institute of Toxicology, Republic of Korea
  3. [HI20C0437]
  4. [1711159820]
  5. [1711133843]

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The study found that low-dose exposure to BPA can lead to abnormal formation of the renal proximal tubules and increased oxidative stress, resulting in decreased renal function. This suggests that although BPA does not exhibit life-threatening toxicity, long-term exposure to low levels of BPA may have negative effects on renal proximal tubular function in humans.
The kidney proximal tubule is responsible for reabsorbing water and NaCl to maintain the homeostasis of the body fluids, electrolytes, and nutrients. Thus, abnormal functioning of the renal proximal tubule can lead to life -threatening imbalances. Bisphenol A (BPA) has been used for decades as a representative chemical in household plastic products, but studies on its effects on the kidney proximal tubule are insufficient. In this study, immu-nocytochemical and cytotoxicity tests were performed using two-and three-dimensional human renal proximal tubular epithelial cell (hRPTEC) cultures to investigate the impact of low-dose BPA (1-10 mu M) exposure. BPA was found to interfere with straight tubule formation as observed by low filamentous actin formation and reduced Na+/K+-ATPase expression in the tubules of hRPTEC 3D cultures. Similar results were observed in rat pup kidneys following oral administration of 250 mg/kg BPA. Moreover, the expression of HO-1 and 8-OHdG, key markers for oxidative stress, was increased in vitro and in vivo following BPA administration, whereas that of OAT1 and OAT, important transporters of the renal proximal tubules, was not altered. Overall, no-observed -adverse-effect-level (NOAEL)-dose BPA exposure can decrease renal function by promoting abnormal tubular formation both in vitro and in vivo. Therefore, we propose that although it does not exhibit life-threatening toxicity, exposure to low levels of BPA can negatively affect homeostasis in the body by means of long-term deterioration of renal proximal tubular function in humans.

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