title: Detoxifying Enzymes at the Cross-Roads of Inflammation, Oxidative Stress, and Drug Hypersensitivity: Role of Glutathione Transferase P1-1 and Aldose Reductase.
abstract: Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivity.
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Sánchez-Gómez
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Díez-Dacal
authors.affiliation: Department of Pharmacology, University of Extremadura Cáceres, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.affiliation: Department of Pharmacology, University of Extremadura Cáceres, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), and Grupo de Hepatología Molecular, Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ) Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Pajares
authors.affiliation: Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Pérez-Sala
keywords: aldose reductase; allergy; detoxification; drug adduct; drug hypersensitivity; glutathione transferase; inflammation; oxidative stress