The impact of dietary nitrates and acrylamide intake on systemic redox status in healthy young adults.

OBJECTIVES: The nitrogen-containing xenobiotics, such as nitrates and acrylamide may potentially influence systemic redox status and contribute to the generation of oxidative stress (OS) in the human body, but there is still a lack of studies that would evaluate the various parameters assessing the oxidative-antioxidant balance. The aim of this study was to evaluate the exposure to nitrates and acrylamide derived from daily diet and to analyze the impact of these nitrate-containing xenobiotics on the parameters of systemic redox status in healthy young adults. MATERIAL AND METHODS: To assess nitrate and acrylamide intake in the study population, a semi-quantitative food frequency questionnaire was used. Systemic redox status was evaluated by measurement of a panel of biochemical parameters: enzymatic (glutathione S-transferase, glutathione reductase, glutathione peroxidase [GPx]) and non-enzymatic (uric acid, bilirubin and albumin), thiol/disulphide homeostasis parameters (total thiol, native thiol, and disulfide) and oxidative/ antioxidant balance indicators (total antioxidant status, total oxidant status, OS index). RESULTS: The average consumption of nitrates and acrylamide in the study population was 1.24 mg/kg b.w./day and 0.23 µg/kg b.w./day, respectively, which is within the normal value range. Of 12 measured parameters, significant differences were revealed for disulfide and total thiol levels, which were increased in the subgroup with the highest daily intake of nitrates compared to the subgroup with the lowest intake; for GPx, which was highest in the subgroup of the lowest daily intake of acrylamide; and for native thiols in the subgroup with the highest daily intake. CONCLUSIONS: The intake of nitrogen-containing xenobiotics within the range considered as normal does not markedly influence redox state parameters in healthy young adults. Some significant changes were revealed only for thiol/disulphide homeostasis parameters, which may be the first line of antioxidant defense, as well as for GPx activity. Compensative mechanisms in healthy young people are efficient enough to neutralize OS induced by slightly increased exposure to nitrogen-containing xenobiotics delivered with food. Int J Occup Med Environ Health. 2023;36(6):773-87.

Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing-Remitting Multiple Sclerosis.

We aimed to investigate the extent of alterations in the pro/antioxidant balance in the blood of patients with relapsing-remitting multiple sclerosis (RRMS) in relation to drug-modified therapy, gender, disability score, and disease duration. 161 patients (67 men and 94 women, aged 24-69 years, median 43.0) and 29 healthy individuals (9 men and 20 women, aged 25-68 years, median 41.0) were included in the study. We measured the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) as well as the concentration of interleukin-6 (IL-6), lipid peroxidation parameters (LPO), total oxidant status (TOS), and total antioxidant capacity (TAS). The activity of SOD did not show any significant differences between patients with RRMS and the control group in our study. In contrast, significant decreased GPx activity and increased CAT activity was observed in the blood of patients with RRMS compared to the control group. Additionally, the activity of CAT was influenced by gender and the use of disease-modifying therapies. Disease-modifying therapies also affected the concentration of TOS, TAS, and LPO. Our studies indicated that enhancing GPx activity may be more beneficial to providing potential therapeutic strategies aimed at modulating antioxidant defenses to mitigate oxidative stress in this disease.

Evaluation of Selected Oxidant/Antioxidant Parameters in Patients with Relapsing-Remitting Multiple Sclerosis Undergoing Disease-Modifying Therapies.

The aim of this study was to evaluate oxidative stress parameters, specifically the concentration of advanced oxidation protein products (AOPP) and ferric-reducing antioxidant power (FRAP), in the serum of patients with relapsing-remitting multiple sclerosis (RRMS). We also analyzed the relationships between each parameter and selected clinical/laboratory multiple-sclerosis-related parameters. The study group comprised 204 patients with RRMS and 29 healthy, age-matched controls. The concentration of AOPP was significantly higher in the RRMS patients than in controls. ROC analysis showed the ability of AOPP to distinguish between the patients with RRMS and controls (the value of AUC was 94.8%, with a sensitivity of 89.69% and specificity of 89.3%). AOPP and FRAP were significantly higher in male than in female RRMS patients. Correlations were found between AOPP and the laboratory markers of inflammation. AOPP differed in the subgroups of patients treated with particular medications. Our findings indicate an increase in the markers of oxidative stress in the serum of RRMS patients, possibly linked with chronic inflammation. Gender and type of treatment affected the markers of oxidative stress.

Role of Sirtuins in Physiology and Diseases of the Central Nervous System.

Silent information regulators, sirtuins (SIRTs), are a family of enzymes which take part in major posttranslational modifications of proteins and contribute to multiple cellular processes, including metabolic and energetic transformations, as well as regulation of the cell cycle. Recently, SIRTs have gained increased attention as the object of research because of their multidirectional activity and possible role in the complex pathomechanisms underlying human diseases. The aim of this study was to review a current literature evidence of SIRTs' role in the physiology and pathology of the central nervous system (CNS). SIRTs have been demonstrated to be crucial players in the crosstalk between neuroinflammation, neurodegeneration, and metabolic alterations. The elucidation of SIRTs' role in the background of various CNS diseases offers a chance to define relevant markers of their progression and promising candidates for novel therapeutic targets. Possible diagnostic and therapeutic implications from SIRTs-related investigations are discussed, as well as their future directions and associated challenges.

Evaluation of Pro/Antioxidant Imbalance in Blood of Women with Polycystic Ovary Syndrome Based on Determination of Oxidized Low-Density Lipoproteins and Ferric Reducing Ability of Plasma Values.

We investigated selected pro/antioxidant parameters in a group of women with polycystic ovary syndrome (PCOS) divided according to age, body mass index (BMI), waist-to-hip ratio (WHR), homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (Quicki). We chose oxidized low-density lipoproteins (oxLDL-C) as a marker of oxidative stress and the ferric reducing ability of plasma (FRAP) as a marker of antioxidant status. In women with PCOS, the values of BMI, WHR, age and concentration of glucose significantly affected oxLDL-C concentration and FRAP values. FRAP correlated with oxLDL-C level in the whole group and in women who were insulin sensitive (HOMA-IR < 2.0). There was a negative relationship between the concentration of Anti-Müllerian hormone and both oxLDL-C and FRAP. Furthermore, the value of FRAP was inversely correlated with luteinizing hormone (LH), follicle-stimulating hormone (FSH) and androstenedione, whereas it was positively correlated with the LH/FSH ratio. The concentration of oxLDL and the value of FRAP are significantly associated with selected metabolic and hormonal parameters in the course of PCOS.

The Activity of Superoxide Dismutase, Its Relationship with the Concentration of Zinc and Copper and the Prevalence of rs2070424 Superoxide Dismutase Gene in Women with Polycystic Ovary Syndrome-Preliminary Study.

Superoxide dismutase (SOD) is a crucial antioxidant enzyme involved in the antioxidant pathway during both normal cellular metabolism and different pathologic processes. We investigated the activity of the copper (Cu)-zinc (Zn) SOD1 as well as the level of Cu and Zn in the serum of women with polycystic ovary syndrome (PCOS) and control group. Moreover, the prevalence of rs2070424 gene polymorphism of the enzyme in the course of PCOS was evaluated. Significantly lower activity of SOD 1 and Cu, Zn concentration was found in the group of women with PCOS than without the syndrome. Insulin resistance in the group of women with PCOS caused a further SOD1 activity decrease, while Cu concentration and the value of Cu/Zn was increased when compared to women with normal insulin levels. Furthermore, we assessed for the first time the rs2070424 polymorphism of SOD1 in the women with PCOS, and in these patients we detected dominant variant AA (93.3%). Due to a small number of other genotypes, it is difficult to state if lower SOD1 activity was strictly associated with the AA variant or if other factors play a crucial role, but this should be taken into account.

Body Composition and Its Impact on the Hormonal Disturbances in Women with Polycystic Ovary Syndrome.

We investigated the relationship between selected body composition (BC) parameters and included 55 women diagnosed with PCOS and 29 women in which PCOS was excluded. Hormone concentration and BC parameters were assessed during hospitalization. Women with PCOS had higher concentration of luteinizing hormones, total testosterone, androstenedione, and Anti-Müllerian hormones compared to women that were not diagnosed with PCOS. We did not observe any significant differences in the BC parameters between both groups as well as between four PCOS phenotype subgroups. Only in the group of women with PCOS was the concentration of sex hormone binding globulin and free testosterone correlated with all investigated BC parameters. Correspondence analysis did not confirm unambiguously associations between phenotypes of PCOS and the value of BC parameters, while logistic regression revealed that increased Anti-Müllerian hormone concentration and the value of body mass index could be useful parameters in differentiating women with PCOS and women with other disorders. The ROC analysis performed on the entire group of women also confirmed that the concentration of Anti-Müllerian hormones could be a powerful parameter to categorize women as suffering from PCOS.

The Associations between Sex Hormones and Lipid Profiles in Serum of Women with Different Phenotypes of Polycystic Ovary Syndrome.

We aimed to evaluate the relationship between selected serum sex hormones and lipid profiles in a group of women with polycystic ovary syndrome (PCOS) dividing according to four phenotypes, value of body mass index (BMI), and presence of hyperlipidemia. The study included 606 Caucasian women. Lipids and selected hormones were estimated using commercially available procedures during hospitalization in 2017. Phenotype of PCOS, BMI value, and hyperlipidemia were significant factors that influenced androgen hormone concentrations, such as total and free testosterone and androstenedione as well as the value of free androgen index (FAI). Moreover, significant changes in concentrations of dehydroepiandrosterone sulphate and sex hormone binding globulin (SHBG) were found between those groups. Higher quartiles of triglyceride concentrations increased the odds ratio of decreased concentrations of SHBG or increased values of FAI, while an adverse relation was found in case of HDL-C. The concentration of estradiol in the blood of women with PCOS was not associated with lipid profile parameters in any investigated groups. Probably, irregularities in sex hormone concentrations during PCOS is not directly associated with lipid profile parameters but could be reflective of the concentration of SHBG or the ratio of SHBG and total testosterone and their association with lipids.

The Impact of Early Pregnancy and Exposure to Tobacco Smoke on Blood Antioxidant Status and Copper, Zinc, Cadmium Concentration-A Pilot Study.

The aim of the study was to evaluate the impact of early pregnancy and exposure to tobacco smoke on antioxidant status and copper, zinc, and cadmium concentrations in the blood of non-smoking and smoking, as well as non-pregnant or pregnant women. The study included 213 women. More specifically, 150 women in first trimester of pregnancy and 63 non-pregnant women. Women were divided into subgroups according to exposure to tobacco smoke. Pregnancy significant influences higher copper and lower zinc concentration in the serum, whereas exposure to tobacco smoke during pregnancy is mainly associated with an elevation in cadmium and zinc concentration. It seems that metallothionein, superoxide dismutase, and glutathione peroxidase are the important antioxidants during early pregnancy, when exposure to tobacco smoke occurs, whereas the pregnancy itself is associated with a higher concentration of metallothionein and activity of catalase. Both pregnancy in the first trimester and exposure to tobacco smoke decrease glutathione concentration. In addition, active and passive maternal smoking have a similarly negative effect on antioxidant status in the first trimester. Early pregnancy as well as exposure to tobacco smoke is associated with significant alteration in antioxidant status and copper, zinc, and cadmium concentration. Due to a small number of smoking subjects (11 cases of non-pregnant, active smokers and 14 pregnant active smokers), the obtained results should be treated as a pilot, and this should be considered for future studies.

The role of proprotein convertase subtilisin/kexin type-9 concentration and paraoxonase 1 activities in the blood of women with polycystic ovary syndrome.

This study aimed to evaluate the concentration of proprotein convertase subtilisin/kexin type-9 (PCSK9) and the activities of paraoxonase 1 in women with and without polycystic ovary syndrome (PCOS). We found significant higher PCSK9, whereas lower high-density lipoprotein concentration in the serum of women with PCOS when compared to the group without PCOS. Also paraoxonase 1 activities were significantly different between women with PCOS than without PCOS. In addition, the women with PCOS and insulin resistance had higher concentrations of PCSK9 than women with PCOS and insulin sensitivity. Higher PCSK9 concentration in the group with PCOS could be also associated with hormones concentrations. Changes in paraoxonase 1 activities and lipid profile parameters as well as higher concentration of PCSK9 in the group of women with PCOS could be associated with metabolism disorders, but due to the small clinical sample size, the study should be continued.

Evaluation of the InterTAK Diagnostic Score in differentiating Takotsubo syndrome from acute coronary syndrome. A single center experience.

BACKGROUND: The aim of this study was to evaluate the usefulness of a novel clinical score - the InterTAK Diagnostic Score in differentiating Takotsubo syndrome (TTS) from acute coronary syndrome (ACS). METHODS: Medical records of 40 consecutive patients with ACS and 20 patients with TTS were managed and retrospectively analyzed at the documented center. Each patient was evaluated using the Inter- TAK Diagnostic Score. To illustrate the diagnostic ability of the score, a receiver operating characteristic (ROC) curve was performed. RESULTS: Takotsube syndrome patients were more often female compared to the ACS group (70% vs. 27.5%, p = 0.002), an emotional trigger was more prevalent among the TTS group (65% vs. 7.5%, p < 0.001). The area under the curve (AUC) for the score was 0.885 (95% confidence interval [CI] 0.78-0.97). Using a cut-off value of 45 points, the sum of sensitivity and specificity was the highest. However, when patients with a score of ≥ 50 were diagnosed as TTS, 85% were diagnosed correctly. When patients with score ≤ 31 were diagnosed as ACS, 92% were diagnosed correctly. CONCLUSIONS: The InterTAK Diagnostic Score might help in differentiating TTS from ACSs with high sensitivity and specificity. This finding requires further investigation to confirm its clinical utility.

Zinc, copper, sirtuin 1 concentration, and glucose metabolism parameters in the blood of women with polycystic ovary syndrome.

The aim of this study was to assess concentration of zinc (Zn), copper (Cu), and sirtuin 1 (SIRT1) in serum of women with polycystic ovary syndrome (PCOS) and their relationships with glucose metabolism parameters. The study included 76 women with PCOS aged between 17 and 39 years old. The blood was collected according to the routine procedure during the follicular phase. Zn and Cu concentrations were performed by flame atomic absorption spectrometry (FAAS). Glucose concentration was estimated by colorimetric methods. Insulin (INs) concentration was determined by enzyme-linked immunosorbent assay. SIRT1 concentration was determined using commercial test. We found higher Cu concentration and Cu/Zn value in the serum of women with PCOS with overweight/obesity. Early stage of insulin resistance (IR) in the group of women with PCOS affected on higher Cu concentration and Cu/Zn value. However, increased value of body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance (HOMA-IR) was not associated with changes in Zn and SIRT1 concentration. Further disturbances in glucose metabolic parameters in the blood of women with PCOS were intensified by overweight/obesity and IR. Overweight/obesity and IR in the women with PCOS increase disorders in Cu homeostasis and glucose metabolism parameters.

The effect of divalent metal chelators and cadmium on serum phosphotriesterase, lactonase and arylesterase activities of paraoxonase 1.

Paraoxonase 1 (PON1) is calcium dependent enzyme involved in many functions in human body. PON1 is synthesized in the liver and secreted to the bloodstream where bounds high-density lipoproteins (HDL). Association of PON1 with HDL increases the enzyme stability and biological activities. PON1 have three different activities: phosphotriesterase, lactonase and arylesterase. Until now there is now commercial available kits to determine these three PON1 activities. Also there is no date about stability of PON1 in serum after storage condition. We have elaborated the optimal conditions for determination of PON1 activities in serum using manual procedure as well as the best storage temperature of human serum for determination of PON1 activities. We have also confirmed that PON1 in serum is associated with HDL. Additionally we have investigated the effect of D-penicillamine, ethylenediaminetetraacetic acid and cadmium chloride on PON1 activities in human serum. D-penicillamine and ethylenediaminetetraacetic acid in therapeutic doses as well as cadmium chloride in toxic doses decrease PON1 activities in human serum when compared to non-treated serum. D-penicillamine as metal chelator inhibits much stronger PON1 activities than ethylenediaminetetraacetic acid.

Changes in lipid profile parameters and PON1 status associated with L55M PON1 polymorphism, overweight and exposure to tobacco smoke.

OBJECTIVE: The aim of our study was to investigate the effects of paraoxonase 1 (PON1) L55M polymorphism on the enzyme's activity and concentration in the serum as well as its association with lipid profile parameters in a group of healthy persons. We also evaluated the presence of PON1 L55M polymorphism in a group of subjects exposed to tobacco smoke and with overweight or obesity on those parameters. METHODS: Analysis of L55M polymorphism was done using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (PCR - RFLP). Serum PON1 concentration and lipid profile parameters were assayed using commercial tests. PON1 activities were measured earlier elaborated procedures. RESULTS: We observed a statistically significant difference in HDL and PON1 concentration: the highest in the LL genotype and the lowest in the MM genotype with the LM genotype having an intermediate concentration. L55M polymorphism influence on PON1 arylesterase and phosphotriesterase activity, whereas PON1 lactonase activity did not differ in all polymorphic variant groups. Exposure to tobacco smoke and overweight or obesity additionally disorder above mentioned parameters. Overweight and obesity in LM and MM genotype could be associated with higher PON1 phosphotriesterase activity. It is also possible that MM genotype could be a determinant of smoking addiction. CONCLUSIONS: L55M polymorphism, like exposure to tobacco smoke and overweight, disorders PON1 status and lipid profile parameters; therefore, it could be a crucial risk factor for the development of many metabolic disorders.

Influence of oral contraceptives on lipid profile and paraoxonase and commonly hepatic enzymes activities.

BACKGROUND: The aim of the study was to verify the influence of oral contraceptives (OCs) on lipid profile and the arylesterase, lactonase and phosphotriesterase activities of paraoxonase 1 (PON1). Also commonly hepatic enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyltranspherase (GGT) were measured. METHODS: Lipid profile and hepatic enzymes were determined using commercial available reagents. Paraoxonase activities were estimated using earlier published procedures. Blood samples were collected from 120 women of similar age (22.6±1.0 years) with similar BMI (20.71±2.20 kg/m2 ). Participations were divided into two groups: 74 females do not take (group A) and 46 women taking OCs (group B). RESULTS: Higher triglycerides and lower low-density lipoproteins levels were observed in group B than in group A) (56.9±19.7 mg/dL. Castelli risk index I was significantly higher in group B when compared to group A (P<.0001), whereas we did not observe any statistically significant differences in Castelli risk index II value between studied groups. In group B, increase in ALT, AST and GGT activities were found, while the de Ritis ratio was lower in group B than in group A. In group B, lower phosphotriesterase activity and higher arylesterase and lactonase activities were found when compared to group A. CONCLUSION: Higher ALT, AST and GGT activities in serum as well as changes in lipid profile and PON activities can indicate that OCs usage can cause disorder in these parameters in the serum of women taking OCs.

The effect of passive and active exposure to tobacco smoke on lipid profile parameters and the activity of certain membrane enzymes in the blood of women in the first trimester of pregnancy.

The effect of tobacco smoke on lipid peroxidation, the lipid profile and membrane-bound enzymatic activity in the first trimester of pregnancy was investigated. In the plasma of women with active exposure to tobacco smoke, we have found increased lipid peroxidation and higher total concentrations of cholesterol, triglycerides and low-density lipoproteins in the blood, as well as a decreased concentration of high-density lipoproteins. A higher concentration of low-density lipoproteins and a lower concentration of high-density lipoproteins were also found in the plasma of passive smokers. In contrast, women who smoked before pregnancy had only a higher low-density lipoprotein concentration. In the group of active and passive smoking women, lower arylesterase and phosphotriesterase activities of paraoxonase were observed, while the lactonase activity of paraoxonase decreased only in the group of active smoking women. In women with active exposure to tobacco smoke, a higher activity level of alanine aminopeptidase and γ-glutamyltransferase in the plasma was found. It is important to monitor the lipid profile during pregnancy, especially when exposure to tobacco smoke occurs.

The role of metallothionein in oncogenesis and cancer treatment.

Metallothionein is cysteine-rich low molecular mass protein. The involvement of MT in many physiological and pathophysiological processes such as apoptosis, proliferation, angiogenesis, and the detoxification of heavy metals suggested participation of this protein in carcinogenesis and tumor therapy. Depending on the type of tissue and classification of carcinoma various it was observed relation between MT expression and tumor type, stage, grade, poor prognosis and body resistance to radiotherapy and chemotherapy. MT in tumor cell plays important role in defense mechanism against the effect of radiation by inhibiting the processes that lead to the apoptosis. A number of studies have shown an increased expression of MT in various human tumors of larynx, pancreas, kidney, uterus and breast, whereas lower MT expression was detected in liver tumors. Variable MT expression was detected in case of thyroid, prostate, lung, stomach and central nervous system tumors. Also MT plays crucial role in the cytostatics treatment. MT can bind cis-platinum compounds and removes them from the cells, which may lead to multidrug resistance. However, the same functions of MT protect against the negative effects of chemotherapeutic treatment. It is especially important in case of heart cells. Analysis of MT expression in tumor cells may be useful in choosing method of treatment. It is difficult to determine whether increased expression of MT is only a inducing factor of the development of the carcinogenesis, its malignances and multidrug resistance, or it is a factor inhibiting the induction and development of cancer.

How Does Tobacco Smoke Affect Fetal Growth Potential in the First Trimester of Pregnancy as Measured by Volume Parameters of the Fetus, Trophoblast, and Gestational Sac?

We aimed to assess if tobacco smoke, as measured by the serum concentration of cotinine and blood concentration of cadmium, influences the fetal, sac, and trophoblast volume in the first trimester of pregnancy. We enrolled women in weeks 11 to 14 of pregnancy: 35 smokers, 24 passive smokers, and 98 nonsmoking healthy women. We found that the fetus volume was similar in all groups (18.70 ± 6.29, 17.11 ± 5.4, 18.97 ± 7.55 cm3). The trophoblast was significantly smallest in smokers (50.27 ± 19.56, 56.71 ± 23.50, 61.95 ± 22.94 cm3). The trophoblast volume was correlated with cotinine and cadmium concentration ( r = -0.54, r = -0.44). In passive smokers, gestational sac and trophoblast volume grew systematically and were correlated with the mean parental height. In smokers, only the gestational sac grew systematically and was correlated with the mean parental height. The fetus volume was independent of mean parental height and intensity of exposure to tobacco smoke. Volumetric changes of the fetus, trophoblast, and sac may be observed in the first trimester; however, their consequences require further research.

The impact of environmental and biological factors on paraoxonase 1 and γ-glutamyltranspeptydase activities in the blood of smelters.

Disorders of paraoxonase and γ-glutamyltranspeptydase activities can induce development of the atherosclerotic process. The aim of the study was to examine the effect of occupational exposure to heavy metals, tobacco smoke and alcohol consumption on the activities of paraoxonase and γ-glutamyltranspeptydase as well as glutathione concentration. We have observed reduced paraoxonase activity and higher γ-glutamyltranspeptydase activity in serum of smelters when compared to control groups. In the blood of smoking smelters was demonstrated a negative correlation between paraoxonase activity and BMI value as well as between paraoxonase activity and tobacco smoke and consumption of 40% alcohol. Also, negative correlation was found for the activity of paraoxonase and glutathione concentration as well as γ-glutamyltranspeptydase activity. Higher γ-glutamyltranspeptydase activity and lower paraoxonase activity in the serum of smelters exposed to heavy metals and tobacco smoke can cause disorders in functioning of the body.

Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.