RADIOPROTECTION OF VASCULAR ENDOTHELIUM IN CANCER TREATMENT: EVALUATION OF EXPERIMENTAL INHIBITORS OF NADPH OXIDASES

LEONARDO SALVARREDI; LUCIANA MAZZEI; ISABEL QUESADA; MARÍA SOLEDAD ALVAREZ; CLAUDIA CASTRO

SAN JUAN

Congreso; XLI REUNIÓN ANUAL DE LA SOCIEDAD DE BIOLOGÍA DE CUYO; 2023

The primary challenge of oncological radiotherapy is to maximize damage to cancerous tissue while minimizing harm to healthytissue. One of the healthy tissues particularly sensitive to radiation and substantially affected by ionizing radiation (IR) is thevascular endothelium (VE). Reactive Oxygen Species (ROS) play a crucial role in radiation-induced vascular damage. Over timeafter irradiation, high levels of ROS have persistently been observed to continue damaging DNA regardless of the initial stimulus.This indicates the presence of an endogenous source of ROS that generates chronic oxidative stress. One of the primary contributorsto endogenous ROS is the activity of NADPH oxidases (NOX). Based on the aforementioned, we raise the question of whetherselective inhibition of NOX could reverse the damage to the vascular endothelium (VE) caused by ionizing radiation (IR). Humanumbilical vein endothelial cells (HUVECs) were irradiated with escalating doses of X-rays (0, 4 and 8 Gy). Superoxide generationwas measured by fluorescence techniques using 10 uM dihydroethidium (DHE) and flow cytometry. We found that thefluorescence intensity of DHE was significantly and sustained increased after 1, 3 and 6 days after irradiation in a dose responsemanner (p