LEPTIN AS A BIOMARKER OF METABOLIC DISORDERS AND OBESITY IN PATIENTS WITH ACUTE HERBICIDE POISONING BASED ON 2,4-DICHLOROPHENOXYACETIC ACID

Bubalo N. M., Balan G. M., Zhminko P. G., Prodanchuk M. G., Kravchuk O. P., Rashkivska I. O., Usenko T. V., Bubalo V. O., Kolyanchuk Y. V., Kolesnyk S. D., Petroshenko G. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Metabolic syndrome and obesity are pathological statuses widespread in the world. Some pesticides are known to increase the risk of developing metabolic disorders and obesity. The aim of this study was to investigate the serum leptin content in 23 patient long-term after acute 2,4 D poisoning, depending on trophological status and to determine its diagnostic and prognostic significance. Serum leptin content, lipoproteins level and trophological status (waist circumference, body mass index) were studied in patients. The level of leptin was increased in almost all persons and especially in persons who had hepatosteatosis and obesity. In persons without hepatosteatosis moderately manifest excess body weight – BMI on average 31,1 ± 2,5, waist circumference – 87,7 cm. At the same time, in persons with hepatosteatosis, the indicators of trophological status were much higher – BMI averaged 42,75 ± 2.39 (p <0.05), waist circumference 116.9 ± 5.95 cm (p <0.05). It was revealed, that persons who suffered acute 2,4-D poisoning with the development of hepatosteatosis and obesity in the remote period, leptin content was almost 2.5 times higher than in the comparison group (p <0.05) and patients after 2,4-D poisoning without liver damage and without signs of hepatosteatosis (p <0.05). Determining the strength of the relationship between leptin content elevation in persons undergoing acute 2,4-D herbicide poisoning with hepatosteatosis and obesity in the remote period and anthropometric parameters and dyslipoproteinemia has a direct positive correlation (r = 0.72 and 0.64; 0.62 and 0.76, respectively). This study has shown that the assessment of leptin levels can be used as biomarker of metabolic disorders, caused by the influence of obesogenic-pesticides.

leptin, obesity, metabolic syndrome, pesticides, poisoning

1. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433-8. DOI: 10.1161/01. CIR.0000111245.75752.C6
2. Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. Jama. 2015;313(19):1973- 4. DOI: 10.1001/jama.2015.4260
3. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR, Lee DH, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocrine reviews. 2012;33(3):378-455. Available from: https://doi.org/10.1210/er.2011-1050
4. Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al. Metabolism disrupting chemicals and metabolic disorders. Reproductive toxicology. 2017;68:3-33. DOI: 10.1016/j.reprotox.2016.10.001
5. Beausoleil C, Ormsby JN, Gies A, Hass U, Heindel JJ, Holmer ML, et al. Low dose effects and non-monotonic dose responses for endocrine active chemicals: science to practice workshop: workshop summary. Chemosphere. 2013;93(6):847-56. Available from: https://doi.org/10.1016/j. chemosphere.2013.06.043
6. Lee DH, Porta M, Jacobs DR, Vandenberg LN. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocrine reviews. 2014;35(4):557-601. DOI: 10.1210/er.9013-1084
7. Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. The Journal of Alternative & Complementary Medicine. 2002;8(2):185-92. DOI: 10.1089/107555302317371479
8. Grun F. Obesogens. Current opinion in endocrinology, diabetes and obesity. 2010;17(5):453-9. DOI: 10.1097/MED.0b013e32833ddea0
9.  Xiao X, Sun Q, Kim Y, Yang SH, Qi W, Kim D, et al. Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice. Food and chemical toxicology. 2018;111:405-16. DOI: 10.1016/j.fct.2017.11.047
10. Tayeb W, Nakbi A, Cheraief I, Miled A, Hammami M. Alteration of lipid status and lipid metabolism, induction of oxidative stress and lipid peroxidation by 2, 4-dichlorophenoxyacetic herbicide in rat liver. Toxicology mechanisms and methods. 2013;23(6):449-58. DOI: 10.3109/15376516.2013.780275
11. Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, et al. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PloS one. 2009;4(4):e5186. DOI: 10.1371/journal.pone.0005186
12. Karmanova DS, Chesnikova LA, Kasirov SI. Vliianie netoksichnyh doz gerbicida 2,4-D na dinamiku massy tela jyvotnyh v eksperimente. Orenbujskii medicinskii vesnik. 2015;3:203-6. [in Russian].
13. Blüher M, Mantzoros CS. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism. 2015;64(1):131-45. Available from: https://doi.org/10.1016/j.metabol.2014.10.016
14. Fietta P, Delsante G. Focus on adipokines. In Theoretical biology forum. 2013;1-2:103-29.
15. McMillen IC, Edwards LJ, Duffield J, Muhlhausler BS. Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction. 2006;131(3):415-27. Available from: https://doi.org/10.1530/rep.1.00303
16. Shimizu H, OH S, Okada S, Mori M. Leptin resistance and obesity. Endocrine journal. 2007;54(1):17-26. Available from: https://doi.org/10.1507/ endocrj.KR-85
17.  Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines: the missing link between insulin resistance and obesity. Diabetes & metabolism. 2008;34(1):2-11. Available from: https://doi.org/10.1016/j.diabet.2007.09.004
18. Blüher M. Adipose tissue dysfunction in obesity. Experimental and Clinical Endocrinology & Diabetes. 2009;117(06):241-50. DOI: 10.1055/s0029-1192044
19. Ghantous CM, Azrak Z, Hanache S, Abou-Kheir W, Zeidan A. Differential role of leptin and adiponectin in cardiovascular system. International journal of endocrinology [Internet]. 2015:534320. Available from: http://dx.doi.org/10.1155/2015/534320
20. Laubner K, Kieffer TJ, Lam NT, Niu X, Jakob F, Seufert J. Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic β-cells. Diabetes. 2005;12:3410-7. Available from: https://doi.org/10.2337/diabetes.54.12.3410
21. Howell IIIG, Mangum L. Exposure to bioaccumulative organochlorine compounds alters adipogenesis, fatty acid uptake, and adipokine production in NIH3T3-L1 cells. Toxicology in Vitro. 2011;25(1):394-402. Available from: https://doi.org/10.1016/j.tiv.2010.10.015
22. Svingen T, Ramhøj L, Mandrup K, Christiansen S, Axelstad M, Vinggaard AM, et al. Effects on metabolic parameters in young rats born with low birth weight after exposure to a mixture of pesticides. Scientific reports. 2018;8(1):305. Available from: https://doi.org/10.1038/s41598- 017-18626-x
23. Sasso M, Beaugrand M, De Ledinghen V, Douvin C, Marcellin P, Poupon R. Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound in medicine & biology. 2010;36(11):1825-35. Available from: https://doi.org/10.1016/j. ultrasmedbio.2010.07.005

«Bulletin of problems biology and medicine» Issue 3 (152), 2019 year, 84-88 pages, index UDK 612.018:616-008.9:613.25:615.9.

10.29254/2077-4214-2019-3-152-84-88