Variability of the Genes Involved in the Cellular Redox Status and Their Implication in Drug Hypersensitivity Reactions

Abstract

Adverse drug reactions are a major cause of morbidity and mortality. Of the great diversity of drugs involved in adverse drug reactions, the most frequent are non-steroidal anti-inflammatory drugs followed by -lactam antibiotics. The redox status regulates the level of reactive oxygen and nitrogen species (RONS). RONS interplay and modulate the action of diverse biomolecules, such as inflammatory mediators and drugs. In this review, we address the role of the redox status in the initiation, as well as in the resolution of inflammatory processes involved in drug hypersensitivity reactions. We summarize the association findings between drug hypersensitivity reactions and variants in the genes that encode the enzymes related to the redox system such as enzymes related to glutathione: Glutathione S-transferase (GSTM1, GSTP, GSTT1) and glutathione peroxidase (GPX1), thioredoxin reductase (TXNRD1 and TXNRD2), superoxide dismutase (SOD1, SOD2, and SOD3), catalase (CAT), aldo-keto reductase (AKR), and the peroxiredoxin system (PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, PRDX6). Based on current evidence, the most relevant candidate redox genes related to adverse drug reactions are GSTM1, TXNRD1, SOD1, and SOD2. Increasing the understanding of pharmacogenetics in drug hypersensitivity reactions will contribute to the development of early diagnostic or prognosis tools, and will help to diminish the occurrence and/or the severity of these reactions.

Antioxidant and anti-stress properties of postbiotics produced by Lysinibacillus macroides G117

“…In detail, CAT can inhibit ROS production directly, and act as antioxidant enzyme [64] . SOD has three forms, SOD1, SOD2, and SOD3, which decompose superoxide free radicals in the cytoplasm, mitochondria, and extracellular fluid, respectively, and are important antioxidant enzymes [65] . MDA, which is produced by the peroxidation of polyunsaturated fatty acids, is also an important marker of oxidative stress [ 66 , 67 ].…”

Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features

“…The gene encoding for catalase (CAT), a crucial endogenous antioxidant enzyme which detoxifies hydrogen peroxide (H 2 O 2 ), is located on chromosome 11 (11p13) ( 52 ). The rs1001179 (C262T) variant in the promoter region of the CAT gene causes alteration at the transcription factor binding site ( 53 , 54 ). The variant T allele seems to confer enhanced transcriptional rate, while data concerning the influence of the rs1001179 on enzyme activity are controversial ( 55 ).…”

“…This genetic variant is associated with altered enzyme activity and may potentially influence a person's antioxidant capacity. In particular, the minor T (Leu) allele has been associated with decreased GPx1 activity ( 54 , 59 – 61 ). To the author's knowledge, this is the first study investigating the relationship of the GPX1 rs1050450 variant and migraine phenotypes.…”

Association of Oxidative-Stress-Related Gene Polymorphisms with Pain-Related Temporomandibular Disorders and Oral Behavioural Habits

“…Rs1050450 is linked to altered enzyme activity and may have an impact on an individual’s antioxidant capability. The minor T allele has been linked to lower GPX1 activity [ 49 ]. This polymorphism has been linked to a number of diseases, including peripheral neuropathy, cardiovascular illness, and migraine [ 45 , 50 , 51 ].…”