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      Long-Term Consequences of Fetal and Neonatal Nicotine Exposure: A Critical Review

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          Abstract

          Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy (NRT) has been developed as a pharmacotherapy for smoking cessation and is considered to be a safer alternative for women to smoking during pregnancy. The safety of NRT use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring, such as impaired fertility, type 2 diabetes, obesity, hypertension, neurobehavioral defects, and respiratory dysfunction. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health.

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          Most cited references147

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          In utero programming of chronic disease.

          1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.
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            Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells.

            Antioxidant enzyme expression was determined in rat pancreatic islets and RINm5F insulin-producing cells on the level of mRNA, protein, and enzyme activity in comparison with 11 other rat tissues. Although superoxide dismutase expression was in the range of 30% of the liver values, the expression of the hydrogen peroxide-inactivating enzymes catalase and glutathione peroxidase was extremely low, in the range of 5% of the liver. Pancreatic islets but not RINm5F cells expressed an additional phospholipid hydroperoxide glutathione peroxidase that exerted protective effects against lipid peroxidation of the plasma membrane. Regression analysis for mRNA and protein expression and enzyme activities from 12 rat tissues revealed that the mRNA levels determine the enzyme activities of the tissues. The induction of cellular stress by high glucose, high oxygen, and heat shock treatment did not affect antioxidant enzyme expression in rat pancreatic islets or in RINm5F cells. Thus insulin-producing cells cannot adapt the low antioxidant enzyme activity levels to typical situations of cellular stress by an upregulation of gene expression. Through stable transfection, however, we were able to increase catalase and glutathione peroxidase gene expression in RINm5F cells, resulting in enzyme activities more than 100-fold higher than in nontransfected controls. Catalase-transfected RINm5F cells showed a 10-fold greater resistance toward hydrogen peroxide toxicity, whereas glutathione peroxidase overexpression was much less effective. Thus inactivation of hydrogen peroxide through catalase seems to be a step of critical importance for the removal of reactive oxygen species in insulin-producing cells. Overexpression of catalase may therefore be an effective means of preventing the toxic action of reactive oxygen species.
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              Type 2 diabetes-a matter of beta-cell life and death?

              In type 2 diabetes, the beta cells of the pancreas fail to produce enough insulin to meet the body's demand, in part because of an acquired decrease in beta-cell mass. In adults, pancreatic beta-cell mass is controlled by several mechanisms, including beta-cell replication, neogenesis, hypertrophy, and survival. Here, I discuss evidence supporting the notion that increased beta-cell apoptosis is an important factor contributing to beta-cell loss and the onset of type 2 diabetes. Interestingly, a key signaling molecule that promotes beta-cell growth and survival, insulin receptor substrate 2 (IRS-2), is a member of a family of proteins whose inhibition contributes to the development of insulin resistance in the liver and other insulin-responsive tissues. Thus, the IRS-2 pathway appears to be a crucial participant in the tenuous balance between effective pancreatic beta-cell mass and insulin resistance.
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                Author and article information

                Journal
                Toxicol Sci
                toxsci
                toxsci
                Toxicological Sciences
                Oxford University Press
                1096-6080
                1096-0929
                August 2010
                2 April 2010
                2 April 2010
                : 116
                : 2
                : 364-374
                Affiliations
                [* ]Reproductive Biology Division, Department of Obstetrics and Gynecology
                []Department of Medicine, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5
                Author notes
                [1 ]To whom correspondence should be addressed. Fax: +905-524-2911. E-mail: hollow@ 123456mcmaster.ca .
                Article
                10.1093/toxsci/kfq103
                2905398
                20363831
                00087b64-badf-42be-93af-6058ec37f811
                © The Author 2010. Published by Oxford University Press on behalf of the Society of Toxicology. For permissions, please email: journals.permissions@oxfordjournals.org.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 February 2010
                : 25 March 2010
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                fetal programming of adult disease,smoking cessation,pregnancy,nicotine

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