Scholarly record
CHEMICAL ECOLOGICAL FACTORS AND IMMUNE PROFILE UNDER ALTERED POLYMORPHISM OF XENOBIOTIC DETOXIFICATION GENES
Abstract
Environmental pollution in industrialized regions has a negative impact on public health status. Excessive accumulation of heavy metals in the human body induces disturbances in the adaptation processes to changes in the quality of the environment, including changes in the immune, humoral and nervous regulation, which can lead to the early development of ecologically caused pathologies in children. Purpose of work: to study the peculiarities of the immune profile of the child population in an industrialized region with excessive contamination of biological media with heavy metals (mercury, arsenic) associated with polymorphic variants of candidate genes. Materials and methods: A total of 180 children aged 3 to 6 years were examined. The observation group consisted of 138 children living in conditions of excessive heavy metal haptic load. The comparison group consisted of 42 people living in a conditionally clean area. The content of arsenic in blood and urine, as well as mercury in urine was determined by mass spectrometry with inductively coupled plasma. Determination of CD3+ CD4+-, CD3+CD8+-, CD19+-lymphocytes, carried out by flow cytometry. The phagocytic activity of leukocytes was studied using formalized sheep erythrocytes. The determination of specific IgG to mercury was carried out using an allergosorbent test with an enzyme label. IgG and IgM were determined by Mancini radial immunodiffusion. Identification of single-nucleotide polymorphic variants (SNP) of the xenobiotic detoxification genes GSTA4 (rs3756980) and MTR (rs1805087) was performed by real-time PCR method. The results: The combined haptic load in the territory where the chemical industry is located causes an excessive level of contamination of the biological media of the child population with heavy metals. The content of arsenic and mercury in the urine significantly exceeded the values of these indicators in the comparison group and the reference level (p<0.05). The immune profile of children with excessive levels of contamination of biological media with arsenic and mercury is characterized by deficiency of T-helpers (CD3+CD4+) and cytotoxic T-lymphocytes (CD3+CD8+), reduced immunoregulatory index CD4+/CD8+ in relation to the comparison group (p<0,05). A decrease in the percentage of phagocytosis, phagocytic number, phagocytic index, and absolute phagocytosis indicates an inhibition of the phagocytic activity of leukocytes relative to the comparison group (p<0.05). However, an increased level of IgG and IgM production against the background of an excess of B-lymphocytes (CD19+) shows signs of hyperactivation of the humoral immune response, and an increased level of IgG to mercury indicates the development of hypersensitization to specific haptens in industrially developed regions with an anthropogenically transformed environment. The established changes in the immune regulation of the child population of an industrially developed region with an increased level of contamination of biological media with arsenic and mercury are associated with the C-allele, TC-heterozygous and CC-homozygous genotypes of the GSTA4 gene (rs3756980), as well as the A allele and the AA genotype of the MTR gene (rs1805087) (OR>1, p<0.05). The established features of the imbalance of cellular (deficiency of CD3+CD4+- and CD3+CD8+-, decrease in CD4+/CD8+, inhibition of phagocytosis against the background of excess CD19+-) and humoral (hyperproduction of IgG, IgM and specific IgG to mercury) immunity associated with polymorphic variants of the GSTA4 (rs3756980) and MTR (rs1805087) genes in children with excessive contamination of biological media with arsenic and mercury make it possible to determine a complex of immune and genetic markers of excessive haptic load with heavy metals and can be used to identify early health disorders in the child population in industrialized regions.
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References15
Al Osman M., Yang F., Yaw Massey I. Exposure routes and health effects of heavy metals on children, Biometals, Germany, 2019, vol. 32, i. 4, pp. 563 - 573
Antunes L.A.A., Machado C.M.C., Couto A.C.K. et al. A Polymorphism in the MTRR Gene Is Associated with Early Childhood Caries and Underweight, Caries Research, Switzerland, 2017, vol. 51, i. 2, pp. 102 – 108
Boverhof D.R., Ladics G., Luebke B. et al. Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary, Regulatory Toxicology and Pharmacology, USA, 2014, vol. 68, i. 1, p. 96–107.
Curtis J.M., Grimsrud P.A., Wright W.S. et al. Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction, USA, 2010, vol. 59, i. 5, pp. 1132 - 1142
Dolgikh О.V., Nikonoshina N. A. Guselnikov M. A. In-Vitro Assessment of Hapten-Induced Immune Regulation in Children with Asthenoneurotic Syndrome, Bulletin of Experimental Biology and Medicine, Russia, 2020, vol. 169, i. 5, pp. 661 -664
State reports on the state and protection of the environment of the Irkutsk region for 2010–2019. [Digital resourse]: https://irkobl.ru/sites/ecology/
State reports on the state and protection of the environment of the Russian Federation for 2012–2018. [Digital resourse]: http://www.mnr.gov.ru/docs/gosudarstvennye_doklady/
Jyothi N. R., Farook N. A. M. Mercury Toxicity in Public Health, Heavy Metal Toxicity in Public Health, IntechOpen, UK, 2020, pp. 51 - 57
Li. W.-X., Lv W.-W., Dai S.-X. et al. Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study, Lipids in health and disease, UK, 2015, vol. 14, p. 101
McKee A.S. Fontenot A.P. Interplay of innate and adaptive immunity in metal-induced hypersensitivity, Current Opinion in Immunology, USA, 2016, vol. 42, pp. 25 - 30
Nurchi V.M., Djordjevic A.B., Crisponi G. et al. Arsenic Toxicity: Molecular Targets and Therapeutic Agents, Biomolecules, Switzerland, 2020, vol. 10, i. 2, p. 235
Raza H. Dual Localization of Glutathione S-Transferase in the Cytosol and Mitochondria: Implications in Oxidative Stress, Toxicity and Disease, The FEBS Journal, UK, 2011, vol. 278, i. 22, pp. 4243 – 4251
Savchenko O.V. Environmental heavy metals pollution effect on preschool children's health, Human ecology, Russia, 2018, №3, pp. 16 - 20
Vertinsky A.P. Pollution of the environment by heavy metals in the Russian Federation, Innovation & Investment, Russia, 2020, №1, pp. 232 - 237
Yann J., Galineau J., Hulin A. et al. Health Effects of Ambient Air Pollution: Do Different Methods for Estimating Exposure Lead to Different Results?, Environment International, USA, 2014, vol. 66, pp. 165 - 171
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