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      Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

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          Abstract

          The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking.

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          Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage.

          Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals. In order to prove the importance of using antioxidants in heavy metal poisoning, pertinent biochemical mechanisms for metal-induced oxidative stress should be reviewed.
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            The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes.

            Reactive oxygen species (ROS) are generated as by-products of aerobic respiration and metabolism. Mammalian cells have evolved a variety of enzymatic mechanisms to control ROS production, one of the central elements in signal transduction pathways involved in cell proliferation, differentiation and apoptosis. Antioxidants also ensure defenses against ROS-induced damage to lipids, proteins and DNA. ROS and antioxidants have been implicated in the regulation of reproductive processes in both animal and human, such as cyclic luteal and endometrial changes, follicular development, ovulation, fertilization, embryogenesis, embryonic implantation, and placental differentiation and growth. In contrast, imbalances between ROS production and antioxidant systems induce oxidative stress that negatively impacts reproductive processes. High levels of ROS during embryonic, fetal and placental development are a feature of pregnancy. Consequently, oxidative stress has emerged as a likely promoter of several pregnancy-related disorders, such as spontaneous abortions, embryopathies, preeclampsia, fetal growth restriction, preterm labor and low birth weight. Nutritional and environmental factors may contribute to such adverse pregnancy outcomes and increase the susceptibility of offspring to disease. This occurs, at least in part, via impairment of the antioxidant defense systems and enhancement of ROS generation which alters cellular signalling and/or damage cellular macromolecules. The links between oxidative stress, the female reproductive system and development of adverse pregnancy outcomes, constitute important issues in human and animal reproductive medicine. This review summarizes the role of ROS in female reproductive processes and the state of knowledge on the association between ROS, oxidative stress, antioxidants and pregnancy outcomes in different mammalian species. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys.

              Besides being important occupational hazards, lead and cadmium are nowadays metals of great environmental concern. Both metals, without any physiological functions, can induce serious adverse health effects in various organs and tissues. Although Pb and Cd are non-redox metals, one of the important mechanisms underlying their toxicity is oxidative stress induction as a result of the generation of reactive species and/or depletion of the antioxidant defense system. Considering that the co-exposure to both metals is a much more realistic scenario, the effects of these metals on oxidative status when simultaneously present in the organism have become one of the contemporary issues in toxicology. This paper reviews short and long term studies conducted on Pb or Cd-induced oxidative stress in blood, liver and kidneys as the most prominent target organs of the toxicity of these metals and proposes the possible molecular mechanisms of the observed effects. The review is also focused on the results obtained for the effects of the combined treatment with Pb and Cd on oxidative status in target organs and on the mechanisms of their possible interactions.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                10 June 2020
                June 2020
                : 10
                : 6
                : 892
                Affiliations
                [1 ]Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia; apizent@ 123456imi.hr (A.P.); jkovacic@ 123456imi.hr (J.K.); btariba@ 123456imi.hr (B.T.L.); ibrcic@ 123456imi.hr (I.B.K.); tzivkovic@ 123456imi.hr (T.Ž.S.); asekovanic@ 123456imi.hr (A.S.); torct@ 123456imi.hr (T.O.); nbrajen@ 123456imi.hr (N.B.); ajuric@ 123456imi.hr (A.J.); jurasovic@ 123456imi.hr (J.J.); mpiasek@ 123456imi.hr (M.P.)
                [2 ]Croatian Veterinary Institute, 10000 Zagreb, Croatia; branovic@ 123456veinst.hr
                [3 ]University Hospital Centre, 10000 Zagreb, Croatia; iva.miskulin@ 123456gmail.com (I.M.); lana.skrgatic@ 123456mef.hr (L.Š.)
                [4 ]Merkur University Hospital, 10000 Zagreb, Croatia; sandra.stasenko@ 123456zg.t-com.hr (S.S.); tatjana.mioc@ 123456hotmail.com (T.M.)
                Author notes
                [* ]Correspondence: mlazarus@ 123456imi.hr
                Author information
                https://orcid.org/0000-0003-0216-0166
                https://orcid.org/0000-0002-0389-9029
                https://orcid.org/0000-0001-5908-506X
                https://orcid.org/0000-0002-1151-8839
                https://orcid.org/0000-0002-3183-7327
                Article
                biomolecules-10-00892
                10.3390/biom10060892
                7356311
                32532134
                4975c8e8-61d2-44ab-ad6e-aae430c3500d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 April 2020
                : 09 June 2020
                Categories
                Article

                toxic metals,essential elements,sod,gpx,metallothionein,sparse discriminant analysis,developmental exposure,maternal smoking

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