Objectives: Metallothionein (MT) and two forms of superoxide dismutase (SOD), which are dependent on zinc and copper ions, are involved in defense against the same superoxide anion radicals and are present in extra- and intracellular compartments. The aim of our study was to investigate MT concentration and Cu/Zn SOD activity in the plasma and erythrocyte lysate of the non-smoking and smoking smelters. Material and Methods: The investigations were performed in the blood of 300 male smelters and 100 non-exposed male subjects. We have measured zinc, copper, malondialdehyde (MDA) and MT concentrations as well as SOD activity. Results: We have observed an increase of Cu/Zn coefficient and decrease of Zn/Cu coefficient in the serum of smelters in comparison with the non-smoking control group. Concentration of MDA in the plasma of smelters was higher in comparison with its concentration in the non-smoking control group. The plasma and the erythrocyte lysate MT concentration increased significantly in the whole group of smelters as compared to the non-smoking control group. The mean value of MT concentration in plasma of the smoking smelters was above 2-fold higher than in the non-smoking control group. The activity of Cu/Zn SOD in plasma of the smoking and non-smoking smelters was decreased in comparison with the smoking and non-smoking control groups, respectively. The lowest activity of Cu/Zn SOD, about 2-3‑fold decreased in comparison with the smoking and non-smoking control groups, was detected in plasma of the smelters. An inverse relationship was observed in the erythrocyte lysate. The highest activity of Cu/Zn SOD was reported in the erythrocyte lysate of the smoking smelters and it was about 2-fold higher than in the non-smoking control group. Conclusions: In extracellular environment MT plays a crucial role in comparison with the SOD, while in the intracellular compartment Cu/Zn SOD and MT cooperate with each other.
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Metallothionein (MT) is a low molecular weight cysteine-rich protein with a number of roles in the pro/antioxidant balance and homeostasis of essential metals, such as zinc and copper, and in the detoxification of heavy metals, such as cadmium and mercury. Until now, detection of metallothionein in biological fluids remained difficult because of a lack of a broadly reactive commercial test. Meaningful comparison of the values of metallothionein concentrations reported by different authors using their specific isolation procedures and different conditions of enzyme-linked immunoassay is difficult due to the absence of a reference material for metallothionein. Therefore in the present study, we describe a quantitative assay for metallothionein in biological fluids such as plasma and urine performed by a direct enzyme-linked immunoassay using a commercially available monoclonal mouse anti-metallothionein clone E9 antibody and commercial standards of metallothionein from rabbit liver and a custom preparation of metallothionein from human liver. The sensitivity of the assay for the standard containing two isoforms MT-I and MT-II from human liver was 140 pg/well. The reactivity of the commercial standards and standards containing two isoforms MT-I and MT-II isolated from human liver in our laboratory with a commercial monoclonal mouse anti-metallothionein clone E9 antibody were similar. This suggests that the described ELISA test can be useful for determination of metallothionein concentration in biological fluids. The concentrations of metallothionein in human plasma, erythrocyte lysate and in urine of smoking and non-smoking healthy volunteers are reported. Tobacco smoking increases the extracellular metallothionein concentration (plasma and urine) but does not affect the intracellular concentration (erythrocyte lysate).
For many years arsenic compounds were used in medicine, including treatment of skin diseases, malaria, diabetes, malaria, stomach ulcers, leukemia and in the eighteenth and the nineteenth century formed the basis of contemporary pharmacology. Due to its toxicity and carcinogenic activity, most of the compounds of this element were removed from use. The major cause of human arsenic toxicity is attributed to contamination of potable water from natural geological sources rather than from mining, smelting and agricultural sources (pesticides or fertilizers). Tobacco smoke also contains arsenic compounds. The characteristics of severe acute arsenic toxicity in humans include gastrointestinal discomfort, vomiting, diarrhea, skin lesions or even death. Chronic exposure frequently causes vascoocclusive disease (such as Blackfoot disease), and the development of lung, skin, liver, kidney and bladder cancers. Arsenic is a pro-inflammatory metal and appears to induce oxidative stress, apoptosis, affect cell proliferation and cell cycle progression. Generation of free radicals by arsenic is associated with its genotoxicity and contributes to the development of neoplastic lesions. Exposure to arsenic can also cause damage of the central nervous system, peripheral neuropathies, and behavioral changes. It was shown the association of exposure to arsenic and type 2 diabetes. Compounds with +3 oxidation state are more toxic and can induce tumor development. Arsenic interacts with other heavy metals, e.g. enhances the toxicity of cadmium nephropathy and acts antagonistically relative to selenium. Studies on the mechanism of interacting the toxicity of arsenic in the human body are crucial and point to lack of access to pure potable water in some regions of the world. People should be aware of the risks that are associated with exposure to arsenic because it is ubiquitous in the industry, as well as the environment. Arsenic is also involved in the spread of lifestyle diseases, especially cancer, and diabetes. Therefore, understanding of the mechanisms responsible for toxicity of arsenic compounds is significant.
PL
Arsen od wieków był wykorzystywany w medycynie, między innymi w leczeniu chorób skóry, malarii, cukrzycy, wrzodów żołądka i białaczki, a w XVIII i XIX wieku stanowił podstawę ówczesnej farmakologii. Obecnie, ze względu na jego toksyczne i kancerogenne działanie, większość związków tego pierwiastka została wycofana z użycia. Największym zagrożeniem dla człowieka nadal jest zanieczyszczona arsenem woda pitna oraz przemysł hutniczy. Ekspozycja na związki arsenu skutkuje podrażnieniem żołądkowo-jelitowym, krwiomoczem, wymiotami i biegunką, a także zmianami skórnymi. W skrajnych przypadkach może prowadzić do śmierci. Długotrwałe narażenie najczęściej powoduje choroby naczyń (np. choroba czarnej stopy) i rozwój nowotworów płuc, skóry, wątroby, nerek czy pęcherza moczowego. Arsen jest metalem prozapalnym. Indukuje stres oksydacyjny, apoptozę, wpływa na proliferację komórek oraz na przebieg cyklu komórkowego. Pierwiastek ten indukuje również aterogenezę i prowadzi do różnych chorób układu sercowo-naczyniowego. Ekspozycja na arsen może powodować uszkodzenie ośrodkowego układu nerwowego, a także obwodowe neuropatie i zmiany behawioralne. Generowanie przez arsen wolnych rodników ma związek z jego genotoksycznością i przyczynia się do rozwoju zmian nowotworowych. Według ostatnich badań, arsen stymuluje też rozwój cukrzycy typu 2. Najbardziej kancerogenne są związki arsenu na +3 stopniu utlenienia. Arsen występuje w środowisku zwykle w obecności innych metali ciężkich, co zwiększa ryzyko pojawienia się interakcji pomiędzy nimi. Nasila nefrotoksyczność kadmu i działa antagonistycznie w stosunku do selenu. Badania dotyczące mechanizmu toksycznego oddziaływania arsenu na organizm człowieka są bardzo istotne i zwracają uwagę na problem dostępu do czystej wody pitnej w niektórych rejonach świata. Ludzie powinni być świadomi zagrożeń jakie wiążą się z ekspozycją na arsen, ponieważ jest on wszechobecny zarówno w środowisku naturalnym, jak i w przemyśle.
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.
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