RT Journal Article
T1 Bisphenol A Modulates Autophagy and Exacerbates Chronic Kidney Damage in Mice
A1 Priego, Alberto Ruiz
A1 González Parra, Emilio
A1 Mas, Sebastián
A1 Morgado-Pascual, José Luis
A1 Ruiz-Ortega, Marta
A1 Rayego-Mateos, Sandra
K1 Bisphenol A
K1 Autophagy
K1 Inflammation
K1 Oxidative stress
K1 Fibrosis
K1 Bisfenol A glicidil metacrilato
K1 Autofagia
K1 Inflamación
K1 Estrés oxidativo
K1 Riñón
AB 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. CONCLU SIONS: BPA deregulates autophagy flux and redox protective mechanisms, suggesting a potential mechanism of BPA deleterious effects in the kidney.
PB MDPI
YR 2021
FD 2021-07-03
LK http://hdl.handle.net/10668/4601
UL http://hdl.handle.net/10668/4601
LA en
NO Priego AR, Parra EG, Mas S, Morgado-Pascual JL, Ruiz-Ortega M, Rayego-Mateos S. Bisphenol A Modulates Autophagy and Exacerbates Chronic Kidney Damage in Mice. Int J Mol Sci. 2021 Jul 3;22(13):7189
DS RISalud
RD Apr 5, 2025