“Efecto protector de quercetina sobre la producción de ERO inducidas por desipramina en leucocitos humanos”

BUAY, ANA SOL; BUSTOS, PAMELA SOLEDAD; ORTEGA, MARIA GABRIELA

Congreso; 7ma edición de la Reunion Internacional de Ciencias Farmacéuticas (RICiFa); 2023

RICiFa

Reactive oxygen species (ROS) include free radicals and non-radical oxygen-derived molecules.These are responsible for generating oxidative damage to biomolecules such as DNA, lipids andproteins, producing alterations in their structure and functionality, which favors tumor processes,inflammation and many degenerative diseases. 1,2 Several studies have shown that antidepressants,such as desipramine (DES), have the ability to induce oxidative stress (OS) in different cells andtissues, contributing to some of the side effects that these drugs produce. 3 Based on this, the aimis to find natural antioxidant compounds capable of neutralizing the toxic effects produced byROS. In this sense, flavonoids became very important because they are secondary metabolitessynthesized by plants, which have numerous biological activities, highlighting their antioxidantactivity. Among them we find quercetin (Q), which was obtained from the leaves of Flaveriabidentis (L.) Kuntze. There are numerous reports where Q has manifested the ability to preventROS induced by antibiotics, but until now, there are no precedents of its protective effects againstthe negative effects of antidepressants. 4 Thus, the production of ROS induced by DES 1µM (plasmaconcentration) was evaluated in mononuclear (MN) and polymorphonuclear (PMN) leukocytesisolated from human blood, using the fluorometric H 2 -DCFDA assay. The generation of ROS wasdemonstrated in both cells, observing a significant increase in fluorescence measurement in cellsDES exposed compared to controls cells without inducer. Subsequently, the protective effect of Qand a reference antioxidant, vitamin C (VIT C), was evaluated in MN and PMN leukocytes exposedto DES 1 µM. Half maximal inhibitory concentration (IC 50 ) were estimated for both compounds inthe two types of cells. In MN, the IC 50 values were 3.027 ± 0.009 µM and 5.12 ± 0.06 µM; while inPMN were 4.1 ± 0.1 µM and 7.6 ± 0.2 µM for Q and VIT C, respectively. These results demonstratethat DES at therapeutic doses, could induce oxidative stress in human leukocytes. At the sametime, it was observed that Q is able to prevent the ROS increase induced by DES, being more activethan the reference antioxidant used. Hence, this flavonoid could represent a potential protectiveagent, able to inhibit the production of ROS induced by DES in human leukocytes, contributing tothe development of new pharmacological strategies to reduce the adverse effects manifested bythis antidepressant.