CONICET | Buscador de Institutos y Recursos Humanos

One of the kidney ́s functions consists of filtering the total circulating blood to remove metabolic waste and other toxic substances. For thatreason, tubular epithelial cells, which constitute renal parenchyma, are constantly exposed to high concentrations of these substances that can betoxic for them. Such is the case of oxalate (Oxa), coming from diet or hepatic synthesis, which can generate calcium oxalate crystals in renaltubular lumen causing injuries in epithelium and tubular structures, leading to the development of chronic renal disease. Resveratrol (trans-3,4′,5-trihydroxystlbene, Rsv) is a polyphenolic compound whose main intake sources in humans are grapes, peanuts and wine. It has numerousbeneficial health effects due to its anti-oxidative and anti-inflammatory actions. One of the Rsv mechanisms is through the modulation ofcyclooxygenase 2 (COX2) expression and activity. In our lab, we had demonstrated that COX2 is a survival gene in renal cells subjected to anabrupt osmolarity change. Thus, the aim of the present work is to assess the possible protective effect of this polyphenol on a model of renaltissue damage induced by oxalate in renal collecting duct derived cells and to evaluate the role of COX2 in that process. To do this, MDCK cellswere subjected to high-NaCl media (512 mOsm/kg H2O) for 72h to obtain a differentiated epithelium, then were treated with differentconcentrations of Rsv (0.1, 1, 5 and 10 μM), and, 30 minutes later, with oxalate (1,5 μM). Two controls were used: treatment only with NaCl andtreatment with NaCl and oxalate, both without Rsv. After treatment, cells were collected, counted, the morphology was analyzed by phasecontrast microscopy and the COX2 expression was evaluated by western blot. The treatment with oxalate to the differentiated epithelia inducedcell damage with changes in cell morphology and decreased the cell number, compared to NaCl control. The treatment with Rsv decreased cellnumber and altered cell morphology (form and size) at 5 and 10 μM, compared to NaCl control. Concentration of 0.1 and 1 μM Rsv did notchange the cell number and morphology compared to NaCl control. COX2 expression was decreased by oxalate respect to NaCl control and itwas increased by Rsv in a concentration-dependent manner. According to these results, Rsv would have a protective effect at 0.1 and 1 μMconcentrations, in contrast with Rsv at 5 and 10 μM concentrations, where the protective capacity is not evidenced. The maintenance of adifferentiated epithelial morphology with Rsv 0.1 and 1 μM could explain the Rsv protective effect. However, Rsv 5 and 10 μM did not preservethe morphology and did not protect from oxalate damage. This fact infers the possibility that Rsv acts by different molecular mechanismsdepending on its concentration.