Serum Paraoxonase and Arylesterase activity after acute chlorpyrifos poisoning in rat

Document Type : Original Research

Authors
M. Soodi 1
S. Ghahramani 2
1 Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University
2 Department of Toxicology, Faculty of medical sciences, Tarbiat Modares University
Abstract
Introduction: Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme with both aryl esterase and lactonase activity, and it possesses significant antioxidant and anti-inflammatory properties. PON1 hydrolyzes the active metabolites of several organophosphorus (OP) insecticides, including parathion, diazinon, and chlorpyrifos. This widely studied enzyme is recognized for its protective role against organophosphate poisoning and vascular diseases, as well as its potential as a biomarker for conditions related to oxidative stress, inflammation, and liver disease. However, limited knowledge exists regarding PON1 activity status following acute organophosphate intoxication. The aim of the present study was to investigate changes in serum PON1 activity after acute chlorpyrifos poisoning and its relationship with acetylcholinesterase (AChE) activity.

Method: Rats were orally given a single dose of chlorpyrifos (160 mg/kg), and blood samples were collected before treatment, as well as at 6 and 96 hours post-treatment. We measured serum cholinesterase, paraoxonase, and arylesterase activity of PON1.

Results: Signs of OP poisoning, including miosis, salivation, tremors, fasciculation, and paralysis, were observed following intoxication, accompanied by a significant inhibition of AChE activity. All symptoms resolved after 48 hours, and AChE activity returned to baseline levels at 96 hours. In contrast, paraoxonase and arylesterase activities progressively increased after 6h and 96h treatment respectively.

Conclusion: The results of our study indicated that serum cholinesterase activity and paraoxonase activity negatively associated in OP poisoning. Based on these findings, monitoring paraoxonase activity after OP intoxication may serve as a valuable biomarker for assessing intoxication.

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1. Gorecki L, Soukup O, Korabecny J. Countermeasures in organophosphorus intoxication: pitfalls and prospects. Trends in Pharmacological Sciences. 2022;43(7):593-606.
2. Ganie SY, Javaid D, Hajam YA, Reshi MS. Mechanisms and treatment strategies of organophosphate pesticide induced neurotoxicity in humans: A critical appraisal. Toxicology. 2022;472.
3. Razwiedani LL, Rautenbach P. Epidemiology of Organophosphate Poisoning in the Tshwane District of South Africa. Environ Health Insights. 2017;11:1178630217694149.
4. Précourt L-P, Amre D, Denis M-C, Lavoie J-C, Delvin E, Seidman E, Levy E. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis. 2011;214(1):20-36.
5. Costa LG, Giordano G, Cole TB, Marsillach J, Furlong CE. Paraoxonase 1 (PON1) as a genetic determinant of susceptibility to organophosphate toxicity. Toxicology. 2013;307:115-22.
6. Dardiotis E, Aloizou AM, Siokas V, Tsouris Z, Rikos D, Marogianni C, et al. Paraoxonase-1 genetic polymorphisms in organophosphate metabolism. Toxicology. 2019;411:24-31.
7. Jakubowski H. Proteomic Exploration of Paraoxonase 1 Function in Health and Disease. Int J Mol Sci. 2023;24(9).
8. Marsillach J, Aragonès G, Mackness B, Mackness M, Rull A, Beltrán-Debón R, et al. Decreased paraoxonase-1 activity is associated with alterations of high-density lipoprotein particles in chronic liver impairment. Lipids Health Dis. 2010;9:46.
9. Ellman GL, Courtney KD, Andres Jr V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology. 1961;7(2):88-95.
10. Çakatay U, Kayali R, Uzun H. Relation of plasma protein oxidation parameters and paraoxonase activity in the ageing population. Clinical and Experimental Medicine. 2008;8:51-7.
11. Eckerson HW, Romson J, Wyte C, La Du B. The human serum paraoxonase polymorphism: identification of phenotypes by their response to salts. American journal of human genetics. 1983;35(2):214.
12. Siqueira AA, Cunha AF, Marques GLM, Felippe ISA, Minassa VS, Gramelich T, et al. Atropine counteracts the depressive-like behaviour elicited by acute exposure to commercial chlorpyrifos in rats. Neurotoxicol Teratol. 2019;71:6-15.
13. Lotti M. Clinical toxicology of anticholinesterase agents in humans. Handbook of Pesticide Toxicology. Academic Press, USA, Ed II. 2001;2:1043.
14. Meisinger C, Freuer D, Bub A, Linseisen J. Association between inflammatory markers and serum paraoxonase and arylesterase activities in the general population: a cross-sectional study. Lipids in Health and Disease. 2021;20(1):81.
15. Ponce-Ruiz N, Murillo-González FE, Rojas-García AE, Mackness M, Bernal-Hernández YY, Barrón-Vivanco BS, et al. Transcriptional regulation of human Paraoxonase 1 by nuclear receptors. Chem Biol Interact. 2017;268:77-84.
Pathobiology Reserach
Volume 26, Issue 3
September 2023
Pages 51-56