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Relationship between internal and external factors and the activity of PON1

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Abstract

Paraoxonase 1 (PON1) is an A-esterase calcium-dependent enzyme that is associated with high-density lipoprotein (HDL) and capable of hydrolyzing a wide variety of substrates, including organophosphate (OP) pesticides. The PON1 phenotype can be modulated by multiple internal and external factors, thereby affecting the catalytic capacity of the enzyme. The aim of this study was to evaluate factors that could modulate PON1 activity in a sample occupationally exposed to pesticides. A cross-sectional, descriptive, and analytical study was carried out with 240 workers. The participants were stratified according to their level of pesticide exposure as reference, moderate-exposure, and high-exposure groups. PON1 activities (arylesterase/AREase, CMPAase, and ssPONase (salt-stimulated)) were determined by spectrophotometry, and the Q192R and L55M PON1 genotypes by real-time PCR. The most frequent genotypes were heterozygous (QR) and homozygous (LL) for PON1Q192R and PON1L55M polymorphisms, respectively. The internal factors associated with the activity of PON1 were the PON1 genotypes (55 and 192) and biochemical parameters related to the lipid profile, in contrast, various external factors related to diet and harmful habits as well as with exposure to pesticides were associated with the activity of PON1. However, using a multivariate mixed ordinal regression model, we found a significant reduction of ssPONase activity in the high-exposure group compared with the reference group only in haplotypes QQLL and RRLL.

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References

  • Androutsopoulos VP, Kanavouras K, Tsatsakis AM (2011) Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases. Toxicol Appl Pharmacol 256:418–424

    CAS  Google Scholar 

  • Aslan M, Kosecik M, Horoz M, Selek S, Celik H, Erel O (2007) Assessment of paraoxonase and arylesterase activities in patients with iron deficiency anemia. Atherosclerosis 191:397–402

    CAS  Google Scholar 

  • Aviram M, Rosenblat M (2005) Paraoxonases and cardiovascular diseases: pharmacological and nutritional influences. Curr Opin Lipidol 16:393–399

    CAS  Google Scholar 

  • Bazzano LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L, Whelton PK (2001) Legume consumption and risk of coronary heart disease in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 161:2573–2578

    CAS  Google Scholar 

  • Ben-David M, Elias M, Filippi JJ, Duñach E, Silman I, Sussman JL, Tawfik DS (2012) Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1. J Mol Biol 418:181–196

    CAS  Google Scholar 

  • Bernal-Hernández YY, Medina-Díaz IM, Barrón-Vivanco BS, Robledo-Marenco ML, Girón-Pérez MI, Pérez-Herrera NE, Quintanilla-Vega B, Cerda-Flores R, Rojas-García AE (2014) Paraoxonase 1 and its relationship with pesticide biomarkers in indigenous mexican farmworkers. J Occup Environ Med 56:281–290

    Google Scholar 

  • Billecke S, Draganov D, Counsell R, Stetson P, Watson C, HSU C, La Du BN (2000) Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos. 28:1335–1342

    CAS  Google Scholar 

  • Boshtam M, Razavi AE, Pourfarzam M, Ani M, Naderi GA, Basati G, Mansourian M, Dinani NJ, Asgary S, Abdi S (2013) Serum paraoxonase 1 activity is associated with fatty acid composition of high-density lipoprotein. Dis Markers 35:273–280

    CAS  Google Scholar 

  • Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 69:541–550

    CAS  Google Scholar 

  • Costa LG, Giordano G, Furlong CE (2011) Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: The hunt goes on. Biochem Pharmacol 81:337–344

    CAS  Google Scholar 

  • Costa LG, Giordano G, Cole TB, Marsillach J, Furlong CE (2013) Paraoxonase 1 (PON1) As a genetic determinant of susceptibility to organophosphate toxicity. Toxicology 307:115–122

    CAS  Google Scholar 

  • Deakin SP, James RW (2004) Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 107:435–447

    CAS  Google Scholar 

  • Eckerson HW, Wyte CM, La Du BN (1983) The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 35:1126–1138

    CAS  Google Scholar 

  • Ferré N, Camps J, Fernández-Ballart J, Arija V, Murphy MM, Ceruelo S, Biarnés E, Vilella E, Tous M, Joven J (2003) Regulation of serum paraoxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem 49:1491–1497

    Google Scholar 

  • Ferretti G, Bacchetti T (2012) Effect of dietary lipids on paraoxonase-1 activity and gene expression. Nutr Metab Cardiovasc Dis. 22:88–94

    CAS  Google Scholar 

  • Fuhrman B, Volkova N, Aviram M (2010) Pomegranate juice polyphenols increase recombinant paraoxonase-1 binding to high-density lipoprotein: studies in vitro and diabetic patients. Nutrition 26:359–366

    CAS  Google Scholar 

  • Furlong CE, Richter RJ, Seidel SL, Motulsky AG (1988) Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon. Am J Hum Genet 43:230–238

    CAS  Google Scholar 

  • Furlong CE, Cole TB, Jarvik GP, Costa LG (2002) Pharmacogenomic considerations of the paraoxonase polymorphisms. Pharmacogenomics 3:341–348

    CAS  Google Scholar 

  • Gokce B, Gencer N, Arslan O, Karatas MO, Alici B (2016) In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1). J Enzyme Inhib Med Chem 31:534–537

    CAS  Google Scholar 

  • Gupta N, Gill K, Singh S (2009) Paraoxonases: structure, gene polymorphism & role in coronary artery disease. Indian J Med Res 130:361–368

    CAS  Google Scholar 

  • Hernández-Avila M, Romieu I, Parra S, Hernández-Avila J, Madrigal H, Willett W (1998) Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City. Salud Publica Mex 39:133–140

    Google Scholar 

  • Hofmann JN, Keifer MC, Checkoway H, De Roos AJ, Farin FM, Fenske RA, Richter RJ, van Belle G, Furlong CE (2010) Biomarkers of sensitivity and exposure in Washington State pesticide handlers. Adv Exp Medi Biol 660:19–27

    CAS  Google Scholar 

  • Juszczuk-Kubiak E, Bujko K, Cymer M, Wicińska K, Gabryszuk M, Pierzchała M (2016) Effect of inorganic dietary selenium supplementation on selenoprotein and lipid metabolism gene expression patterns in liver and loin muscle of growing lambs. Biol Trace Elem Res 172:336–345

    CAS  Google Scholar 

  • Kim DS, Burt AA, Ranchalis JE, Richter RJ, Marshall JK, Nakayama KS, Jarvik ER, Eintracht JE, Rosenthal EA, Furlong CE, Jarvik GP (2012) Dietary cholesterol increases paraoxonase 1 enzyme activity. J Lipid Res 53:2450–2458

    CAS  Google Scholar 

  • Liao F, Zhu XY, Wang YM, Zhao YS, Zhu LP, Zuo YP (2007) Correlation of serum arylesterase activity on phenylacetate estimated by the integrated method to common classical biochemical indexes of liver damage. J Zhejiang Univ Sci B 8:237–241

    CAS  Google Scholar 

  • Lixandru D, Mohora M, Coman A, Stoian I, van Gils C, Aerts P, Manuel-y-Keenoy B (2010) Diet and paraoxonase 1 enzymatic activity in diabetic foot patients from romania and belgium: favorable association of high flavonoid dietary intake with arylesterase activity. Ann Nutr Metab 56:294–301

    CAS  Google Scholar 

  • Lou-Bonafonte JM, Gabás-Rivera C, Navarro MA, Osada J (2015) PON1 and Mediterranean diet. Nutrients 7:4068–4092

    Google Scholar 

  • Mackness M, Mackness MB (2015) Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene 567:12–21

    CAS  Google Scholar 

  • Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA (1996) Paraoxonase: biochemistry, genetics and relationships to plasma lipoproteins. Curr Opin Lipidol 7:69–76

    CAS  Google Scholar 

  • Mackness B, Davies GK, Turkie W, Lee E, Roberts DH, Hill E, Roberts C, Durrington PN, Mackness MI (2001) Paraoxonase status in coronary heart disease are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol 21:451–1457

    Google Scholar 

  • Marsillach J, Ferré N, Vila MC, Lligoña A, Mackness B, Mackness M, Deulofeu R, Solá R, Parés A, Pedro-Botet J, Joven J, Caballeria J, Camps J (2007) Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease. Clin Biochem 40:645–650

    CAS  Google Scholar 

  • Medina-Díaz IM, Ponce-Ruiz N, Ramírez-Chávez B, Rojas-García AE, Barrón-Vivanco BS, Elizondo G, Bernal-Hernández YY (2016) Downregulation of human paraoxonase 1 (PON1) by organophosphate pesticides in HepG2 cells. Environ Toxicol 32:450–500

    Google Scholar 

  • Messina V (2014) Nutritional and health benefits of dried beans. Am J Clin Nutr 100(Suppl 1):437S–442S

    CAS  Google Scholar 

  • Peou S, Milliard-Hasting B, Shah SA (2016) Impact of avocado-enriched diets on plasma lipoproteins: a meta-analysis. J Clin Lipidol 10:161–171

    Google Scholar 

  • Pérez Méndez O, García Hernández L (2007) High–density lipoproteins (HDL) size and composition are modified in the rat by a diet supplemented with “Hass” avocado (Persea americana Miller). Arch Cardiol Mex 77:17–24

    Google Scholar 

  • Précourt LP, Amre D, Denis MC, Lavoie JC, Delvin E, Seidman E, Levy E (2011) The three-gene paraoxonase family: Physiologic roles, actions and regulation. Atherosclerosis 214:20–36

    Google Scholar 

  • Rajkovic MG, Rumora L, Barisic K (2011) The paraoxonase 1, 2 and 3 in humans. Biochem Med (Zagreb) 21:122–130

    CAS  Google Scholar 

  • Ramírez-Jiménez R, Mejía-Saucedo R, Calderón-Hernández J, Montero-Montoya R, Yáñez-Estrada L (2014) Concentraciones urinarias de metabolitos de plaguicidas organofosforados en niños y adolescentes de una zona agrícola de México Revista Iberoamericana de Ciencias. ReIbCi 1(4):87–97 http://reibci.org/publicados/2014/septiembre/3300123.pdf. Accessed 30 Jan 2019

  • Rao MN, Marmillot P, Gong M, Palmer DA, Seeff LB, Strader DB, Lakshman MR (2003) Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans. Metabolism 52:1287–1294

    CAS  Google Scholar 

  • Richter RJ, Jarvik GP, Furlong CE (2008) Determination of paraoxonase-1 status without the use of toxic organophosphate substrates. Circ Cardiovasc Genet 1:147–152

    CAS  Google Scholar 

  • Rojas-García AE, Solís-Heredia MJ, Piña-Guzmán B, Vega L, López-Carrillo L, Quintanilla-Vega B (2005) Genetic polymorphisms and activity of PON1 a Mexican population. Toxicol Appl Pharmacol 205:282–289

    Google Scholar 

  • Sarandöl E, Serdar Z, Dirican M, Safak O (2003) Effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men. J Nutr Biochem 14:507–512

    Google Scholar 

  • Schrader C, Rimbach G (2011) Determinants of paraoxonase 1 status: genes, drugs and nutrition. Curr Med Chem 18:5624–5643

    CAS  Google Scholar 

  • Sirivarasai J, Kaojarern S, Sura T, Yoovathaworn K (2011) Biochemical, environmental, and genetic factors associated with paraoxonase (PON1) activity. Biochem Genet 49:364–368

    CAS  Google Scholar 

  • Sokoloff K, Frase W, Arbuckle TE, Fisher M, Gaudreau E, LeBlanc A, Morisset A-S, Bouchard MF (2016) Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada-results from the MIREC study. Environ Int 94:133–140

    CAS  Google Scholar 

  • Sözmen EY, Mackness B, Sözmen B, Durrington P, Girgin FK, Aslan L, Mackness M (2002) Effect of organophosphate intoxication on human serum paraoxonase. Hum Exp Toxicol 21:247–252

    Google Scholar 

  • Tanrisev M, Toprak Ö (2004) The relationship of clinical signs with therapy and biochemical parameters in patients with organophosphate intoxication. Eur J Gen Med 1:32–37

    Google Scholar 

  • Valcke M, Samuel O, Bouchard M, Dumas P, Belleville D, Tremblay C (2006) Biological monitoring of exposure to organophosphate pesticides in children living in periurban areas of the province of Quebec, Canada. Int Arch Occup Environ Health 79:568–577

    CAS  Google Scholar 

  • Wafa T, Nadia K, Amel N, Ikbal C, Insaf T, Asma K, Hedi MA, Mohamed H (2013) Oxidative stress, hematological and biochemical alterations in farmers exposed to pesticides. J Environ Sci Health B 48:1058–1069

    CAS  Google Scholar 

  • WHO. (2006) World Health Organization. BMI classification, global database on body mass index. http://apps.who.int/bmi/index.jsp?introPage=intro_3.html. Accessed 30 January 2019.

  • WHO. (2010) World Health Organization. The WHO recommended classification of pesticides by hazard and guidelines to classification 2009. http://apps.who.int/iris/bitstream/10665/44271/1/9789241547963_eng.pdf. Accessed 30 January 2019.

  • Worek F, Mast U, Kiderlen D, Diepold C, Eyer P (1999) Improved determination of acetylcholinesterase activity in human whole blood. Clin Chim Acta 288:73–90

    CAS  Google Scholar 

  • Yildiz A, Sezen Y, Gur M, Yilmaz R, Demirbag R, Erel O (2008) Association of paraoxonase activity and coronary collateral flow. Coron Artery Dis 19:441–447

    Google Scholar 

  • Zhang X, Sui H, Li H, Zheng J, Wang F, Li B, Zhang Y (2014) Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers exposed to organophosphate pesticides. Exp Biol Med (Maywood) 239:232–223

    Google Scholar 

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Acknowledgments

We are grateful to all the workers who participated in the study. The authors also thank Dr. Leticia Yáñez-Estrada and her team at the Autonomous University of San Luis Potosí, Mexico for measurements of DAP.

Funding

This work was supported by CONACyT (Grant no. 233803).

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Authors and Affiliations

  1. Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado, Universidad Autónoma de Nayarit, Ciudad de la Cultura s/n, Col. Centro, C.P, 63000, Tepic, Nayarit, Mexico

    María del Carmen Xotlanihua-Gervacio, José Francisco Herrera-Moreno, Irma Martha Medina-Díaz, Yael Yvette Bernal-Hernández, Briscia S. Barrón-Vivanco & Aurora Elizabeth Rojas-García

  2. Posgrado en Ciencias Biológico Agropecuarias, Unidad Académica de Agricultura, Km. 9 Carretera Tepic – Compostela, Xalisco, Nayarit, Mexico

    María del Carmen Xotlanihua-Gervacio & José Francisco Herrera-Moreno

  3. Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Cuernavaca, Morelos, Mexico

    Stephen J. Rothenberg

Authors
  1. María del Carmen Xotlanihua-Gervacio
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  2. José Francisco Herrera-Moreno
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  3. Irma Martha Medina-Díaz
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  4. Yael Yvette Bernal-Hernández
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  5. Stephen J. Rothenberg
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  6. Briscia S. Barrón-Vivanco
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  7. Aurora Elizabeth Rojas-García
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Correspondence to Aurora Elizabeth Rojas-García.

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This study was approved by the Bioethics Commission of Nayarit State, Mexico (CEBN/0112017).

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del Carmen Xotlanihua-Gervacio, M., Herrera-Moreno, J.F., Medina-Díaz, I.M. et al. Relationship between internal and external factors and the activity of PON1. Environ Sci Pollut Res 26, 24946–24957 (2019). https://doi.org/10.1007/s11356-019-05696-9

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