Investigation of paraoxonase 1 activity of the workers at the plant, who have long-term contact with organophosphorus compounds

Cover Page

Abstract


Background. Liver enzyme paraoxonase 1 (PON1) plays an important role in protection the organism from toxic effects of organophosphorus compounds (OPs) via their hydrolysis whose rate and efficiency depend on PON1 serum level activity. PON1 activity is largely determined by the polymorphic variants of the PON1 gene. Effect of long-term work with exposure to the toxic OPs on the PON1 activity is almost unknown. The aim of the present work was to study the effect of long-term work with exposure to the toxic OPs on PON1 serum enzymatic activity depending on polymorphisms Q191R, L54M, C(-108)T PON1 gene.

Materials and methods. PON1 serum enzymatic activity and PON1 polymorphisms were determined in men, who were categorized in 2 groups: workers of companies providing storage and disposal of the OPs (68) and control group (37). The PON1 191, PON1 55 and PON1 108 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. PON1 serum enzymatic activity was measured by a spectrophotometric method using paraoxon.

Results. PON1 activity in workers with exposure to the toxic OPs relative was increased compared to the control group (p = 0,027). Differences in serum PON1 activity was shown for the carriers of certain genotypes of the PON1 gene: PON1 serum activity was higher in workers compared to controls only for LL genotype (L54M polymorphism) and C allele (C(-108)T polymorphism) carriers (p < 0,001 and p = 0,002, correspondently).

Conclusion. We suggest that the increase in serum PON1 activity in workers providing storage and disposal of OPs could be modulated with the polymorphic variants of the PON1 gene.


Natalia D Razgildina

Author for correspondence.
razgnata@mail.ru
B.P. Konstantinov Nuclear Physics Institute in Saint Petersburg
Russian Federation, Gatchina, Russia

Senior laboratory, Molecular and Radiation Biophysics Department

Valentina V Miroshnikova

mutantropol@mail.ru
B.P. Konstantinov Nuclear Physics Institute in Saint Petersburg
Russian Federation, Gatchina, Russia

Researcher, Molecular and Radiation Biophysics Department

Aleksey V Fomichev

fomichoff74@mail.ru
S.M. Kirov Military Medical Academy
Russian Federation, Saint Petersburg, Russia

Senior lecturer, Department of military field therapy

Ekaterina V Malisheva

katerinamalisheva@mail.ru
S.M. Kirov Military Medical Academy
Russian Federation, Saint Petersburg, Russia

Intern doctor, Department of military field therapy

Alexandra A Panteleeva

aleksandra9122@mail.ru
B.P. Konstantinov Nuclear Physics Institute in Saint Petersburg
Russian Federation, Gatchina, Russia

Trainee researcher, Molecular and Radiation Biophysics Department

Sofia N Pchelina

sopchelina@hotmail.com
B.P. Konstantinov Nuclear Physics Institute in Saint Petersburg
Russian Federation, Gatchina, Russia

Head of the laboratory, Molecular and Radiation Biophysics Department

  • Кабачник М.И. Химия фосфорорганических соединений. Избранные труды: В 3 т. – М.: Наука, 2008. [Kabachnik MI. Chemistry of organophosphorus compounds. Selected works. In 3 vol. Moscow: Science; 2008. (In Russ.)]
  • Голофеевский В.Ю., Фомичев А.В., Халимов Ю.Ш., и др. Эндоскопические и морфологические особенности патологии желудка и двенадцатиперстной кишки у лиц, занятых на работах с фосфорорганическими соединениями // Профилактическая медицина. – 2014. – Т. 15. – С. 605–619. [Golofeevsky VY, Fomichev AV, Khalimov YuSh, et al. Endoscopic and morphological features of pathology of the stomach andduodenum at the persons which were involved in works with organophosphorus compounds. Prophilakticheskaya Medicina. 2014;15:605-619. (In Russ.)]
  • Mazur A. An enzyme in the animal organism capable of hydrolyzing the phosphorus-fluorine bond of alkyl fluorophosphates. J Biol Chem. 1946;164:271-289.
  • Rajkovic MG, Rumora L, Barisic K. The paraoxanase 1, 2 and 3 in humans. Biochem Ved. 2011;21:122-130. doi: 10.11613/BM.2011.020.
  • Deakin S, Leviev I, Gomataschi M, et al. Enzymatically active paraoxanase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem. 2002;277:4301-4308. doi: 10.1074/jbc.M107440200.
  • Leviev I, Negro F, James RW. Two alleles of the human paraoxonase gene produce different amounts of mRNA. An explanation for differences in serum concentrations of paraoxonase associated with the (Leu-Met54) polymorphism. Arterioscler Thromb Vasc Biol. 1997;17:2935-2939. doi: 10.1161/01.ATV.17.11.2935.
  • Leviev I, James RW. Promoter polymorphisms of human paraoxonase PON1 geneand serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol. 2000;20:516-521. doi: 10.1161/01.ATV.20.2.516.
  • Hotopf M, Mackness MI, Nikolau V, et al. Paraoxonase in Gulf War veterans. J Occup Environ Med. 2003;5:668-675. doi: 10.1097/01.jom.0000071506.96740.39.
  • Синицкий М.Ю., Волобаев В.П., Асанов М.А. Частота микроядер в лимфоцитах шахтеров с различными полиморфными вариантами генов репарации двойных разрывов ДНК // Экологическая генетика. – 2015. – Т. 13. – № 4. – С. 30–33. [Sinitckiy MY, Volobuev VP, Asanov MA. The frequency of micronuclei in lymphocytes miners with different polymorphic variants of gene repair of double breaks of DNA. Ekologicheskaja genetika. 2015;13(3):30-33. (In Russ.)]
  • Akhmedova (Pchelina) S, Anisimov S, Yakimovsky A, Schwartz E. Gln-Arg 191 polymorphism of paraoxonase and Parkinson’s disease. Human Heredity. 1999;49:178-180. doi: 10.1159/000022868.
  • Akhmedova (Pchelina) S, Yakimovsky A, Schwartz E. Paraoxonase 1 Polymorphism Met-Leu 54 Is Associated with Parkinson’s Disease. Journal of Neurological Sciences. 2001;184:179-182. doi: 10.1016/S0022-510X(01)00439-7.
  • Пчелина С.Н., Кудинов С.В., Беркович О.А., и др. Ассоциация структурных полиморфизмов промоторной области и кодирующей части гена параоксоназы с развитием инфаркта миокарда у мужчин до 45 лет // Медицинский академический журнал. – 2003. – Т. 2. – № 3. – С. 58–64. [Pchelina SN, Kudinov SV, Berkovic OA, et al. Association of structural polymorphisms in the promoter region and in the coding portion of the paraoxonase gene with development of myocardial infarction in men under 45 years. Medicinsky Academichesky Journal. 2003;2(3):58-64. (In Russ.)]
  • Geldmacher-von Mallinckrodt M, Diepgen TL. The human serum paraoxonase — polymorphism and specificity. Toxicol Environ Chem. 1988;18:179-196. doi: 10.1080/02772248809357310.
  • Davies H, Richter RJ, Kiefer M, et al. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet. 1996;14:334-6. doi: 10.1038/ng1196-334.
  • Suheiro T, Nakamura T, Inoue M, et al. A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression. Atherosclerosis. 2000;150:295-298. doi: 10.1016/S0021-9150(99)00379-2.
  • Brophy VH, Jampsa RL, Clendenning JB, et al. Effects of 5′ regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet. 2001;68:1428-1436. doi: 10.1086/320600.
  • Mackness B, Durrington PN, Mackness MI. Human serum paraoxonase. Gen Pharmacol. 1998a;31: 329-336. doi: 10.1016/S0306-3623(98)00028-7.
  • Lacasana M, Lopez-Flores I, Rodriguez-Barranco M, et al. Interaction between organophosphate pesticide exposure and PON1 activity on thyroid function. Toxicol Appl Pharmacol. 2010;249:16-24. doi: 10.1016/j.taap.2010.07.024.
  • da Silva J, Moraes CR, Heuser SR, et al. Evaluation of genetic damage in a Brazilian population occupationally exposed to pesticides and its correlation with polymorphisms in metabolising genes. Mutagenesis. 2008;23:415-422. doi: 10.1093/mutage/gen031.
  • Lee BW, London L, Poulauskis J, et al. Association between human paraoxonase gene polymorphism and chronic symptoms in pesticide exposed workers. J Occup Environ Med. 2003;45:118-122. doi: 10.1097/01.jom.0000052953.59271.e1.
  • Hernández AF, Mackness B, Rodrigom L, et al. Paraoxonase activity and genetic polymorphisms in greenhouse workers with long term pesticide exposure. Hum Exp Toxicol. 2003;22:565-574. doi: 10.1191/0960327103ht400oa.
  • Lee PC, Rhodes SL, Sinsheimer JS, et al. Functional paraoxonase 1 variants modify the risk of Parkinson’s disease due to organophosphate exposure. Environ Int. 2013;56:42-47. doi: 10.1016/j.envint.2013.03.004.
  • Alonso-Navarro Н, Himenez-Jimenez FJ, Garcia-Martin E, et al. Genomic and pharmacogenomic biomarkers of Parkinson’s disease. Curr Drug Metab. 2014;15: 129-81. doi: 10.2174/138920021502140327175404.
  • Menini T, Gugliucci A. Paraoxonase 1 in neurological disorders. Redox Rep. 2010;19:49-58. doi: 10.1179/1351000213Y.0000000071.
  • Haley RW, Billecke S, La Du BN. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicol Appl Pharmacol. 2000;157:227-33. doi: 10.1006/taap.1999.8703.

Supplementary files

Supplementary Files Action
1. Fig. 1. Serum PON1 activity levels in the group of workers at the plant providing storage and disposal OPs and in the control group. The x-axis – study groups; y-axis – the PON1 activity (nmol ∙ min) / mL View (21KB) Indexing metadata
2. Fig. 2. Serum PON1 activity levels among carriers of LL genotype (L54M) of PON1 gene. The x-axis – study groups; y-axis – the PON1 activity (nmol ∙ min) / mL View (29KB) Indexing metadata
3. Fig. 3. Serum PON1 activity levels among carriers of C allele (C(-108)T) of PON1 gene. The x-axis – study groups; y-axis – the PON1 activity (nmol ∙ min) / mL View (30KB) Indexing metadata

Views

Abstract - 161

PDF (Russian) - 94


Copyright (c) 2017 Razgildina N.D., Miroshnikova V.V., Fomichev A.V., Malisheva E.V., Panteleeva A.A., Pchelina S.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.