Trostchansky Vasconcellos, Andrés Ezequiel

Research interests

Our research builds upon previous studies investigating the role of reactive oxygen species and nitrogen in various pathological conditions where oxidative stress plays a crucial role. In addition to this, we have extended our investigation into other domains of knowledge, including chemical synthesis and the evaluation of novel antiplatelet compounds. We have also focused on the phytochemical characterization of natural extracts derived from plants and fruits, examining their biological role in both in vitro and in vivo settings.
Central to our work are the antioxidant properties of nitric oxide (NO) and the formation of nitrogenated lipids, particularly nitro derivatives (NO2-R). By modifying oxidative agents of arachidonic acid (AA), such as through the nitration of AA (NO2-AA), we can generate novel chemical species with specific bioactivities, thereby altering conventional signaling pathways. Our hypothesis revolves around the notion that nitrated derivatives of AA can function as intermediaries in cell signaling during inflammatory processes while also serving as indicators of oxidative damage. We have directed our attention to several target enzymes, including prostaglandin endoperoxide synthase (PGHS), responsible for the initial oxidation step of AA; lipoxygenase (LOX), involved in the synthesis of leukotrienes (pro-inflammatory) or specialized pro-resolving lipids (SPM); phagocytic NADPH oxidase (NOX2); protein kinase C (PKC); and Protein Disulfide Isomerase (PDI). These enzymes are associated with various cell types, signaling pathways, and their involvement in human pathology's inflammatory processes. Our focus lies in studying the impact of NO2-AA on enzyme activity, elucidating the biological significance of these effects, and unraveling the underlying biochemical mechanisms. Our investigation encompasses a diverse range of study systems, including a) cell cultures, b) animal models, and c) human samples, to delve into the aforementioned aspects. Moreover, we have extended our research to incorporate additional biological models, such as olives, and more recent additions like cow's milk and tomato extracts. Through our research endeavors, we have cultivated collaborations on both national and international scales, collaborating with esteemed institutions like the Faculty of Agronomy, INIA, LATU, as well as partners in Brazil, Chile, Spain, and the United States.
Another area of focus within our research relates to Protein Disulfide Isomerase (PDI), a chaperone that plays a role in the assembly of NOX2 and platelet aggregation. The presence of a dithiol CHGC motif in its active site renders it susceptible to modification by NO2-AA or other agents capable of covalently interacting with dithiols. Over the past seven years, we have dedicated our efforts to developing compounds with the ability to modulate PDI activity, thereby inhibiting undesired platelet aggregation. As an illustration, we have obtained a patent for a peptide with a sequence identical to the active site of PDI, which effectively inhibits both PDI activity and platelet aggregation. The significance of our studies on PDI modification lies in its involvement in inflammatory processes, particularly within the phagocytic response, as well as its connection to dysfunctional platelet aggregation in thrombotic events. In collaboration with a research group in Chile, we are presently engaged in the design and synthesis of chemical compounds with antiaggregant properties. Our work encompasses the entire spectrum, starting from the chemistry involved in creating compounds with diverse scaffold structures and extends to exploring the biological aspects of these compounds. To assess their efficacy, we employ techniques such as HPLC and LC-MS analysis, which allow us to determine both the chemical composition and biological activity of the compounds.
One current significant area of our research focuses on lipidomics studies, where we investigate the lipid composition and analyze the presence, absence, or alterations in levels of various lipid mediators. These analyses encompass a wide range, including the examination of cell membrane composition and the levels of bioactive compounds. Moreover, we extend our lipidomic investigations to the study of diseases which involve inflammatory processes such as aging, frailty or ALS, utilizing animal and human models to identify plasma biomarkers that can aid in the establishment and progression of the disease.
In summary, our research has accumulated extensive experience in measuring the formation of reactive species and characterizing different compounds across various cell types. We have explored the mechanisms of action of lipid-derived products as well as chemically synthesized products. Furthermore, we have honed our expertise in analytical techniques such as TLC, HPLC, and particularly mass spectrometry. Our application of lipidomic studies spans across different cell, animal models and humans allowing us to establish correlations between the levels of lipid-derived products and the initiation, progression, and modulation of diseases, as well as responses to drug treatments.

Working area

nitrated fatty acids, Mass spectrometry, lipidomics, AA metabolism, platelets, oxidant species, PDI, NOX