Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 13, Pages -Publisher
MDPI
DOI: 10.3390/ijms22137189
Keywords
Bisphenol A; autophagy; inflammation; oxidative stress; fibrosis
Funding
- Instituto de Salud Carlos III (ISCIII) [PI17/00119, PI20/00140, DTS20/00083, PI16/01298]
- Instituto de Salud Carlos III (ISCIII) (Red de Investigacion Renal REDINREN) [RD16/0009]
- Fondos FEDER European Union [PI17/00119, PI20/00140, DTS20/00083, PI16/01298]
- Fondos FEDER European Union (Red de Investigacion Renal REDINREN) [RD16/0009]
- Comunidad Autonoma de Madrid FEDER-a way to build Europe [B2017/BMD-3751 NOVELREN-CM]
- Juan de la Cierva incorporacion grant [IJC2018-035187-I]
- Juan de la Cierva de Formacion grant [FJC2019-042028-I]
- Fundacion Conchita Rabago grant
- Convocatoria Dinamizacion Europa Investigacion 2019 MINECO [EIN2019-103294]
- European Union [812699]
- Sociedad Espanola de Nefrologia
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This study demonstrates that chronic exposure to BPA can lead to inflammatory infiltration, tubular injury, and fibrosis in the kidneys of healthy mice, and exacerbation of renal lesions in SNX mice. BPA also modulates the autophagy process and redox protective mechanisms in the kidneys, suggesting potential harmful effects of BPA in the kidneys.
BACKGROUND: Bisphenol A (BPA) is a ubiquitous environmental toxin that accumulates in chronic kidney disease (CKD). Our aim was to explore the effect of chronic exposition of BPA in healthy and injured kidney investigating potential mechanisms involved. METHODS: In C57Bl/6 mice, administration of BPA (120 mg/kg/day, i.p for 5 days/week) was done for 2 and 5 weeks. To study BPA effect on CKD, a model of subtotal nephrectomy (SNX) combined with BPA administration for 5 weeks was employed. In vitro studies were done in human proximal tubular epithelial cells (HK-2 line). RESULTS: Chronic BPA administration to healthy mice induces inflammatory infiltration in the kidney, tubular injury and renal fibrosis (assessed by increased collagen deposition). Moreover, in SNX mice BPA exposure exacerbates renal lesions, including overexpression of the tubular damage biomarker Hepatitis A virus cellular receptor 1 (Havcr-1/KIM-1). BPA upregulated several proinflammatory genes and increased the antioxidant response [Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1) and NAD(P)H dehydrogenase quinone 1 (Nqo-1)] both in healthy and SNX mice. The autophagy process was modulated by BPA, through elevated autophagy-related gene 5 (Atg5), autophagy-related gene 7 (Atg7), Microtubule-associated proteins 1A/1B light chain 3B (Map1lc3b/Lc3b) and Beclin-1 gene levels and blockaded the autophagosome maturation and flux (p62 levels). This autophagy deregulation was confirmed in vitro. CONCLUSIONS: BPA deregulates autophagy flux and redox protective mechanisms, suggesting a potential mechanism of BPA deleterious effects in the kidney.
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