Protective effect of quercetin on reactive oxygen species production induced by desipramine in human leukocytes

ANA SOL BUAY; PAMELA BUSTOS; GABRIELA ORTEGA

Congreso; 7ª Reunión Internacional de Ciencias Farmacéuticas.; 2023

Universidad Nacional de Rosario

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 and proteins, 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 and tissues, contributing to some of the side effects that these drugs produce.3 Based on this, the aim is to find natural antioxidant compounds capable of neutralizing the toxic effects produced by ROS. In this sense, flavonoids became very important because they are secondary metabolites synthesized by plants, which have numerous biological activities, highlighting their antioxidant activity. Among them we find quercetin (Q), which was obtained from the leaves of Flaveria bidentis (L.) Kuntze. There are numerous reports where Q has manifested the ability to prevent ROS induced by antibiotics, but until now, there are no precedents of its protective effects against the negative effects of antidepressants.4 Thus, the production of ROS induced by DES 1µM (plasma concentration) was evaluated in mononuclear (MN) and polymorphonuclear (PMN) leukocytes isolated from human blood, using the fluorometric H2-DCFDA assay. The generation of ROS was demonstrated in both cells, observing a significant increase in fluorescence measurement in cells DES exposed compared to controls cells without inducer. Subsequently, the protective effect of Q and a reference antioxidant, vitamin C (VIT C), was evaluated in MN and PMN leukocytes exposed to DES 1 µM. Half maximal inhibitory concentration (IC50) were estimated for both compounds in the two types of cells. In MN, the IC50 values were 3.027 ± 0.009 µM and 5.12 ± 0.06 µM; while in PMN were 4.1 ± 0.1 µM and 7.6 ± 0.2 µM for Q and VIT C, respectively. These results demonstrate that DES at therapeutic doses, could induce oxidative stress in human leukocytes. At the same time, it was observed that Q is able to prevent the ROS increase induced by DES, being more active than the reference antioxidant used. Hence, this flavonoid could represent a potential protective agent, able to inhibit the production of ROS induced by DES in human leukocytes, contributing to the development of new pharmacological strategies to reduce the adverse effects manifested by this antidepressant.