Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism |
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| Affiliation: | 1. Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain;2. Universidad de Alcalá, Department of Biomedicine and Biotechnology, Alcalá de Henares, Spain;3. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;4. Universidad de Alcalá, Laboratory of Pathophysiology of the Vascular Wall, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, IRICYS, Department of System Biology/Physiology Unit, Alcalá de Henares, Spain;5. University Rey Juan Carlos, Biochemistry and Molecular Biology Area, Department of Basic Sciences of Health, Alcorcon, Spain;6. Clinical Analysis Service, Principe de Asturias Hospital, Alcalá de Henares, Spain;7. Unidad de Investigación Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)/Facultad de Medicina Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain |
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| Abstract: | Bisphenol-A (BPA), a chemical -xenoestrogen- used in the production of the plastic lining of food and beverage containers, is present in the urine of almost the entire population. Recent studies have shown that BPA exposure is associated with podocytopathy, increased urinary albumin excretion (UAE), and hypertension. Since these changes are characteristic of early diabetic nephropathy (DN), we explored the renal effects of BPA and diabetes including the potential role of sexual dimorphism. Male and female mice were included in the following animals' groups: control mice (C), mice treated with 21.2 mg/kg of BPA in the drinking water (BPA), diabetic mice induced by streptozotocin (D), and D mice treated with BPA (D + BPA). Male mice form the D + BPA group died by the tenth week of the study due probably to hydro-electrolytic disturbances.Although BPA treated mice did not show an increase in serum creatinine, as observed in D and D + BPA groups, they displayed similar alteration to those of the D group, including increased in kidney damage biomarkers NGAL and KIM-1, UAE, hypertension, podocytopenia, apoptosis, collapsed glomeruli, as well as TGF-β, CHOP and PCNA upregulation. UAE, collapsed glomeruli, PCNA staining, TGF-β, NGAL and animal survival, significantly impaired in D + BPA animals. Moreover, UAE, collapsed glomeruli and animal survival also displayed a sexual dimorphism pattern.In conclusion, oral administration of BPA is capable of promoting in the kidney alterations that resemble early DN. Further translational studies are needed to clarify the potential role of BPA in renal diseases, particularly in diabetic patients. |
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