Effect of Tributyltin on porcine endothelial cell integrity

OBJECTIVE. Many physiological imbalances are nowadays attributed to toxic compounds widespread in the environment, among these, organotins, including tributyltin (TBT), exert generic cytotoxic effect including oxidative stress but also tissue-specific effects such as endocrine disruptors. TBT was already found in human blood and accumulated in endothelial cells at mitochondrial level. A correlation between TBT and cardiovascular disease it has been hypothesized but incompletely demonstrated. To date very few studies analyzed the specific effects of TBT on endothelial cells, therefore in the present research we evaluated the effect of TBT on porcine aortic endothelial cells (pAECs). MATERIALS AND METHODS pAECs were incubated with increasing dose of TBT (0, 100, 250, 500, 750, 1000 nM) to evaluate cytotoxicity and apoptosis, and with TBT (100, 500 nM) for 1, 7, 15h to study the expression of some genes involved in endothelial integrity and in the inflammatory response. RESULTS: TBT reduced cell viability in a dose dependent manner , the flow cytometric data showed that TBT induced both apoptosis and necrosis with early apoptosis prevalent at the lowest doses and earliest times. Adhesion molecules exhibited a different response to TBT exposure, VCAM-1 was significantly reduced with both TBT concentrations starting from 7 h of exposure, ICAM-1 showed a transient decrease at early times and low dose while P-SEL significantly increased after 15 h of exposure at TBT 500 nM. TBT reduced the expression of molecules involved in cell-to-cell junctions: OCC-1 and ZO-1. IL-6 mRNA was transiently reduced at early times for both TBT doses, while after 15h of exposure at TBT 500 nM the IL-6 expression was significantly increased. CONCLUSIONS: Overall we observed that TBT was toxic to pAECs and showed the ability to deeply interfere with expression of key genes involved in in the control of endothelial integrity.