SP033BISPHENOL A INDUCES AUTOPHAGY AND OXIDATIVE STRESS IN EXPERIMENTAL CHRONIC KIDNEY INJURY AND IN TUBULAR CELLS

Abstract

Introduction and Aims: Uremic toxins accumulated as a result of chronic kidney disease (CKD) contribute to the complications of the disease and its progression. Bisphenol A (BPA) is a ubiquitous environmental toxin accumulated in CKD. Autophagy is a degradative lysosomal process that eliminates misfolded and protein aggregates or damaged organelles to maintain intracellular homeostasis and cellular integrity. Recent evidences suggest that autophagy is implicated in tubular and glomerular cell damage in renal diseases. Nevertheless, the role of autophagy on pathophysiology of renal disease is still unknown. The aim of this study is to explore the role of autophagy as mechanism of BPA toxicity on experimental chronic kidney injury. Methods: The role of BPA in chronic kidney injury was studied in a experimental model of subtotal nephrectomy in mouse c57bl/6. Some animals were injected with BPA (120mg/kg/day) intraperitoneally during 5 weeks. Furthermore, in vitro studies were developed in human proximal tubular epithelial cells (HK-2) stimulated with BPA at different concentrations (100 uM and 200 uM). Gene Expression were measured by qRT-PCR and proteins levels were analyzed by several techniques such as western blot and immunohistochemistry. Results: We observed that in subtotal nephrectomized mice, the BPA exposure during 5 weeks led to oxidative stress, autophagy and inflammation by increasing the gene expression of specific autophagy markers such as Atg5, Atg7, LC3B and Beclin. On the other hand, BPA exposure in mice increased the expression of oxidative stress and Nrf2 target genesas Hemo-oxygenase 1(HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1). Additionally, in cell culture the stimulation with BPA increased in a dose dependent manner the gene expression of proinflamatory factors as CCL-2, CCL-5 and IL-6 and the autophagy markers LC3B and Beclin. Conclusions: These data suggests that BPA causes oxidative stress, inflammation, and autophagy in experimental chronic kidney injury developping a fundamental role into CKD progression.