Molecular Approach of Oxidative Stress and Bronchopulmonary Dysplasia: Relationship of GSTM1 and GSTT1 Genes.

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease, with its own clinical, radiological, and histopathological characteristics, which mainly affects premature newborns (NBs), resulting from a combination of factors that include immaturity, inflammation, and lung injury, in addition to therapy with mechanical ventilation and exposure to high concentrations of oxygen. However, even with advances in care for critically ill NBs, BPD continues to be a challenge for the care team and family members. This has been identified as one of the most important causes of morbidity and mortality due to prematurity and can have significant impacts on the quality of life of the affected patients. While interactions between the risk factors associated with BPD characterize it as multifactorial, its real pathogenesis still remains uncertain, as some NBs, despite having similar risk factors, do not develop it, suggesting, therefore, that susceptibility to BPD is genetically determined. Genetic variants in the glutathione S-transferase Mu-1/glutathione S-transferase theta-1-null (GSTM1/GSTT1) genes may be associated with a greater risk of developing BPD in premature NBs, as they affect the function of glutathione S-transferases (GSTs) enzymes and, consequently, the body's ability to eliminate toxic or harmful pro-inflammatory substances. GSTM1/GSTT1-null individuals, due to the absence of gene expression, present loss of enzymatic activity of the respective GST enzymes, triggering failures in the detoxification process and the consequent development of numerous diseases resulting from oxidative damage such as infertility, chronic kidney disease, eryptosis, retinopathy of prematurity, necrotizing enterocolitis, periventricular leukomalacia, intraventricular hemorrhage. The objective of this narrative review was to highlight the role of genetic variants in the GSTM1/GSTT1 genes in the onset of BPD.