Activity of glutathione S-transferase and its π isoenzyme in the context of single nucleotide polymorphism in the GSTP1 gene (rs1695) and tobacco smoke exposure in the patients with acute pancreatitis and healthy subjects

Abstract

Oxidative stress associated with the course of acute pancreatitis (AP) can cause changes in the involvement of antioxidants, which can result in the increased production of free radicals with pro-inflammatory potential. Through its noncatalytic activity, the glutathione S-transferase and its π isoenzyme (GST-π), apart from cellular xenobiotics detoxification, are involved in the regulation of cellular signalling, metabolism and apoptosis. This study aimed to evaluate the impact of SNP rs1695 in the GSTP1 gene on GST and GST-π activity in healthy subjects and patients with acute pancreatitis (AP). The concentration of glutathione (GSH) as an important component of the antioxidant system, necessary for environmental xenobiotics detoxification by GST, and malonyldialdehyde (MDA) as a marker of oxidative stress induced by inflammation were also assessed. SNP was examined in 39 AP patients and 51 healthy subjects using PCR-RFLP methods. GST activity (in plasma and erythrocyte lysate) and GST-π activity (in erythrocyte lysate) were measured using the spectrophotometric method with 1-chloro-2,4-dinitrobenzene and ethacrynic acid as substrate, respectively. Blood GSH concentration was measured using the Patterson method. Concentrations of high-sensitive C-reactive protein (hs-CRP) and MDA were measured using commercial tests. In the blood of non-smoking AP patients with GG genotypes for SNP rs1695 in the GSTP1 gene, the lowest GST-π activity was shown. It was accompanied by the lowest hsCRP concentration in this group. In the blood of smoking healthy subjects with AG genotype, a decrease in GST-π activity was noted compared to non-smokers from this group. However, in the blood of smokers with AP, a gradually decreasing GST-π activity was noted in individuals with AA genotype, which was associated with the increasing MDA concentration. It confirms the role of GST-π in the neutralization of oxidative stress induced by the exposure to smoke xenobiotics.