A single exposure to the environmental contaminant tributyltin induces oxidative stress and vascular endothelial dysfunction

Organotin compounds, such as tributyltin (TBT), are environmental contaminants known for toxic effects. Subacute exposure to TBT leads to vascular dysfunction associated with increased production of reactive oxygen species (ROS). This study aimed to investigate whether a single exposure to TBT induces endothelial dysfunction. Adult female rats were divided into two groups: control (CT) and TBT-exposed. Vascular reactivity of isolated aortic rings was assessed 24hours after a single oral dose of TBT (500ng/kg). Vasodilator responses to acetylcholine and sodium nitroprusside were not altered by TBT exposure. However, aortic rings from TBT-exposed rats exhibited greater contractile response to phenylephrine and reduced influence of endothelial denudation or L-NAME incubation on vascular reactivity. The impaired nitrergic modulation induced by TBT was prevented by co-incubation with superoxide dismutase plus L-NAME. In vitro DAF-2 assay indicated reduced NO production in the TBT group. TBT-induced vascular hyperreactivity was reversed by incubation with apocynin, TIRON, catalase, allopurinol, losartan, indomethacin, NS-398, SQ-29,548, and SC-19,220. In contrast, the non-selective NOX inhibitor VAS2870 did not modify the response to phenylephrine. Dihydroethidium staining showed increased ROS levels- including superoxide anion and hydrogen peroxide-in aortas from TBT-exposed animals. Scanning electron microscopy revealed endothelial structural damage in the TBT group. Together, these findings indicate that a single dose of TBT (500ng/kg) caused vascular dysfunction, likely resulting from impaired endothelial and nitrergic modulation mediated by increased ROS production derived from xanthine oxidase, activation of the local renin-angiotensin system, and cyclooxygenase pathways in female rats.