Diabetes is one of the most common metabolic disorders and emerges secondary to an interaction between genetic, environmental and lifestyle factors. This work provides an overview of the impact of ...smoking on the development of vascular complications in this condition and also provides an overview of the potential role of smoking in predisposition to diabetes. There are many studies documenting the impact of smoking on health (not focused on patients with diabetes), suggesting that the health exposure in these individuals is at least comparable to that observed in the general population. Distinct studies of smoking in patients with diabetes have unambiguously confirmed an increased prevalence and a higher risk of early death associated with the development of macrovascular complications. Smoking is also associated with premature development of microvascular complications and may contribute to the pathogenesis of type 2 diabetes. It has been shown that smoking is a predictor of the progression of glucose intolerance at both the transition from normoglycaemia to impaired glucose tolerance status and the increased risk of developing diabetes. The mechanisms explaining the relationship between smoking and the development of diabetes are not fully understood, although a number of hypotheses have been put forward. Current evidence indicates that smoking cessation is not only important to prevent macrovascular complications in diabetes, but also has a role in limiting microvascular disease and may also facilitate glycaemic management in this condition.
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.
Display omitted
•A toxic effect of tobacco smoke is elevated in the course of acute pancreatitis (AP).•Smoking increases Cd and MDA concentrations accompanied by decreased GST-π activity.•Smoking contribute to a decreased GST-π activity in patients with the AA genotype.•GG genotype (rs1965,GSTP1) is related with decreased GST-π activity in pancreatitis.
Little is known about the contribution of each of the three superoxide dismutase isozymes (SODs) to the total SOD activity in extracellular fluids. This study was aimed to investigate the alterations ...in concentration/activity of (SODs) in plasma, in context of sex, obesity, exposition to cigarette smoke, and genotypic variability of five selected single nucleotide polymorphisms (SNPs) in genes
,
,
. Men showed higher SOD1 concentration, lower SOD3 concentration and higher total antioxidative capacity (TAC) values. Intersexual variability was observed in concentration of copper, zinc, and cadmium. The obese showed higher total oxidative capacity regardless of sex. An increase in SOD2 activity was coexistent with obesity in men, and exposition to cigarette smoke in non-obese individuals. Additionally, in state of this exposition, Cu,Zn-SOD contribution to the total SOD was lower. Interestingly, over 90% of the obese were of C/T genotype of rs4880 (
). Non-obese of T/T genotype (rs4880) were of lower total SOD activity due to decrease in both Cu,Zn-SOD and Mn-SOD activities. SNP rs2234694 was associated with differences in concentration of SODs, depending on obesity status. Correlations indicate that both TAC and SODs, together, may adapt to insulin resistance and inflammation-derived oxidative stress found in obesity. This topic should be further investigated.
Genetic factors and tobacco smoke exposure can be associated with an increased risk of acute pancreatitis (AP). The pathogenesis of AP is associated with intensive oxidative stress. Glutathione ...peroxidase (GPx) is one of many enzymes involved in the neutralization of free radicals. This study aimed to investigate the impact of SNP rs1050450 in the GPX1 gene and rs713041 in the GPX4 gene on the activity of total GPx in a group of AP patients and healthy subjects. It was found that AP can contribute to decreased GPx activity (in plasma and erythrocyte lysate) accompanied by an increased glutathione reductase (GR) activity and decreased glutathione (GSH) concentration in two groups, non-smokers and smokers. A decreased GPx activity in erythrocyte lysate of AP patients compared to healthy subjects was associated with the occurrence of the CC genotype for SNP rs1050450. It was noted an increased GPx activity and decreased GR activity in erythrocytes of non-smoking AP patients with the TT genotype compared to subjects with the CC and TC genotype for SNP rs713041. However, in the group of smoking AP patients with this genotype, GR activity was elevated compared to non-smokers, which was accompanied by increased GSH concentration. These results can indicate that smoking in the course of AP can change the involvement of antioxidants in dependence on the genotype for the examined SNPs. The CC genotype for SNP rs1050450 and the TT genotype for rs713041 increases the risk of AP recurrence, which may be associated with increased MDA concentration.
Display omitted
•Acute pancreatitis (AP) is associated with the pro/antioxidative imbalance.•AP can contribute to decreased GPx activity in plasma and erythrocytes.•The CC genotype (rs1050450) and the TT genotype (rs713041) increases the risk of AP.•Smoking in AP change the involvement of antioxidants in dependence on the genotype.
Oxidative stress has been implicated in the initiation of acute pancreatitis (AP). HDL is considered to be a preventing factor against cell membrane oxidation, thanks to the presence on its surface ...of apolipoprotein A-I (apoA-I) and paraoxonase-1 (PON1), which activity can be modified by genetic and environmental factors. The impact of SNP rs662 in the PON1 gene and SNP rs670 and rs5069 in the APOAI gene on PON1 activities and its concentration in the population of AP patients and healthy volunteers was investigated. In the group of patients with AP, a decreased HDL concentration and PON1 activities were observed. A decrease in the aryloesterase and lactonase activities of PON1 in AP patients with the TT genotype for SNP rs662 (especially in smokers) was found. In the group of patients with the AA genotype (rs670), the highest concentrations of HDL and apoA-I were observed, which were gradually decreasing in the course of AP. Changes in the concentration of apoA-I were associated with the changes in the concentration and activities of PON1 in the AP patients with the AA genotype for SNP rs670. A decreasing apoA-I concentration contributing to lowering PON1 concentration and its activities during the hospitalization of AP patients with the CC genotype for SNP rs5069 were shown. Therefore, more susceptibility of persons with the CC genotype for SNP rs5069 to pro/antioxidative imbalance was shown. In this process, an important role was played by the HDL level and its interaction with PON1 and apoA-I.
•Influence of xenobiotics on particular Cu,Zn-SOD residues results in its inhibition.•The data regarding some inhibitors lacks research carried out on human Cu,Zn-SOD.•Some Cu,Zn-SOD inhibitors have ...been used in medicine.•There are contradictory data for inhibition of Cu,Zn-SOD by some compounds
The function of Cu,Zn-SOD is to dismutate superoxide into hydrogen peroxide and oxygen. This task is fulfilled due to structural nuances of the enzyme. Many environmental xenobiotics have been proved to inhibit Cu,Zn-SOD. Those compounds could be found not only in industrial sewage, cigarettes and various chemical agents – some of them are used as drugs, drug production substrates or are the product of drug biotransformation. Cu,Zn-SOD exposition to these compounds leads to inhibition due to: copper ion chelation, unfolding the structure of the enzyme, affecting residues vital for activity maintenance. This review covers a selection of Cu,Zn-SOD inhibitors, referring to in vivo and in vitro study.
This study was aimed at evaluating the changes in metallothionein (MT) concentration in the blood of patients with acute pancreatitis (AP) and healthy subjects, taking into account the extracellular ...(plasma) and intracellular (erythrocyte lysate) compartments. The impact of single-nucleotide polymorphisms (SNPs) in the
(rs11640851),
(rs964372) and
(rs10636) genes on MT concentration and their association with the concentration of metals (Cu, Zn, Cd) and ceruloplasmin as Cu-related proteins were analyzed. The concentration of a high-sensitivity C-reactive protein (hs-CRP) and IL-6 as markers of inflammation, and malonyldialdehyde (MDA), superoxide dismutase (SODs) activity and the value of total antioxidant capacity (TAC) as parameters describing the pro/antioxidative balance were also assessed. In the AP patient groups, an increased MT concentration in erythrocyte lysate compared to healthy subjects was shown, especially in individuals with the GG genotype for rs964372 in the
gene. A Zn concentration was especially decreased in the blood of smoking AP patients with the AA genotype for SNP rs11640851 in the
gene and the GC genotype for SNP rs10636 in MT2A, compared to non-smokers with AP, which was accompanied by an increase in the value of the Cu/Zn ratio. The exposure to tobacco smoke xenobiotics increased the risk of AP occurrence in subjects with the CC genotype for SNP rs11640851 in the
gene by more than fourfold. The investigated polymorphisms, rs11640851 in the
gene, rs964372 in the
gene and rs10636 in the
gene, seem to be an important factor in maintaining homeostasis in an organism under oxidative stress conditions.
The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary factors, including ...single-nucleotide polymorphisms (SNPs) of genes for coding insulin, insulin receptors, or insulin receptor substrates (INS, INSR, IRS1, IRS2) or superoxide dismutase isozymes (SOD1, SOD2, SOD3), have been linked with the incidence of obesity and diabetes. However, the underlying changes in the plasma concentration/activity of superoxide dismutase isozymes and their potential connection with the said hereditary factors remain unexplored. Previously, we have observed that the plasma concentration/activity of superoxide dismutase isozymes differs in the context of obesity and/or rs2234694 (SOD1) and rs4880 (SOD2) and that the concentrations of SOD1, SOD2, SOD3 are correlated with each other. Intersexual variability of SOD1 concentration was detected regardless of obesity. In this study, the variability of concentration/activity of superoxide dismutase isozymes in plasma is considered in the context of type 2 diabetes and/or SNPs: rs2234694 (SOD1), rs5746105 (SOD2), rs4880 (SOD2), rs927450 (SOD2), rs8192287 (SOD3). Genotypic variability of SNP rs3842729 (INS), previously studied in the context of insulin-dependent diabetes, is investigated in terms of selected clinical parameters associated with type 2 diabetes. This study revealed higher SOD1 concentration in diabetic men compared to women, and extremely high SOD1 concentration, higher total superoxide dismutase, and copper-zinc superoxide dismutase activity, and lower superoxide dismutase and copper-zinc superoxide dismutase activity (when adjusted for the concentration of SODs) in the diabetic group regardless of sex. Multiple logistic regression, applied to explore possible links between the studied SNPs and other factors with the odds of type 2 diabetes or obesity, revealed that the genotypic variability of rs4880 (SOD2) could affect these odds, supporting the findings of several other studies.
Display omitted
•Higher plasma SOD1 concentration in type 2 diabetes, regardless of sex.•Altered superoxide dismutase activity in type 2 diabetes, regardless of sex.•C/T genotype, rs4880 (SOD2) is associated with odds of obesity or type 2 diabetes.
Doxorubicin (DOX) is one of the most frequently used anticancer drugs in breast cancer treatment. However, clinical applications of DOX are restricted, largely due to the fact that its action ...disturbs the pro/antioxidant balance in both cancerous and non-cancerous cells. The aim of this study was to investigate the influence of fullerene (C
) in cell treatment by DOX on the proliferation of human breast cancer cells (MCF-7), concentration of metallothionein (MT) and superoxide dismutase (SOD), and SOD activity in these cells. The use of C
in complexes with DOX causes a change in the level of cell proliferation of about 5% more than when caused by DOX alone (from 60⁻65% to 70%). The use of C
as a DOX nanotransporter reduced the MT level increase induced by DOX. C
alone caused an increase of SOD1 concentration. On the other hand, it led to a decrease of SOD activity. C
in complex with DOX caused a decrease of the DOX-induced SOD activity level. Exposure of MCF-7 cells to DOX-C
complexes results in a decrease in viable cells and may become a new therapeutic approach to breast cancer. The effects of C
in complexes with DOX on MCF-7 cells included a decreased enzymatic (SOD activity) and nonenzymatic (MT) antioxidant status, thus indicating their prooxidant role in MCF-7 cells.
This study was aimed at evaluating the changes in the concentration and activity of all superoxide dismutase isoenzymes (SOD1, SOD2, SOD3) in the blood of patients with acute pancreatitis (AP) and ...healthy subjects, taking into account the extracellular (plasma) and intracellular (erythrocyte lysate) compartment. The relationships between the activity/concentration of SODs, metal concentration and the markers of inflammation were evaluated. To assess the pro/antioxidative imbalance, the malonyldialdehyde (MDA) concentration and the value of total antioxidant capacity (TAC) were measured. The impact of single-nucleotide polymorphism (SNP) in the SOD1 gene (rs2070424) on the activity/concentration of SOD1 as the main isoenzyme of the SOD family was also analyzed in this study. The SOD2 activity in erythrocytes was increased compared to plasma: 10-fold in the AP patient group and 5-fold in healthy subjects. The plasma of AP patients showed an increased SOD1 concentration and decreased SOD2 and SOD3 concentrations compared to healthy subjects. The Cu/Zn SOD (SOD1 + SOD3) concentration in plasma of AP patients was elevated compared to healthy subjects, but changes in plasma Cu/Zn SOD (SOD1 + SOD3) activity in the examined groups were not observed. An influence of SNP rs2070424 in the SOD1 gene on the total activity of SOD in AP patients (with AG genotype), accompanied by an increased IL-6 concentration, was observed. In oxidative stress conditions induced by inflammation, the participation of individual forms of plasma SOD isoenzymes in total antioxidative activity of SOD changed. A significant increase in the intracellular SOD1 concentration in plasma of AP patients proves the important role of this isoenzyme in the neutralization of oxidative stress induced by impaired Cu and Zn homeostasis. The presence of increased concentration of SOD2 in erythrocytes of healthy subjects and AP patients confirms the important function of this isoenzyme in the antioxidative defense.
PDF
