Toxicology International (Formerly Indian Journal of Toxicology)

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Concentration-Dependent Inhibition of Acetylcholinesterase by Organophosphate Poisoning in Dogs: A Biochemical and Electrocardiograph Study


Affiliations
1 Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
2 Department of Veterinary Medicine, University of Ibadan, Nigeria
     

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Organophosphate poisoning (OP) is one of the most common poisonings in developing countries. In this study, twentyfour dogs in four groups of six each were used. Control group bathed with water only, group B with 16% Coumaphos (recommended), groups C and D with times 10 and 20 of 16% Coumaphos, respectively. Blood was collected from cephalic vein for biochemical assays. Electrocardiographic parameters were assessed from a Lead-II electrocardiogram. There was a significant increase (p<0.05) in total cholesterol in group B and D compared to the control. LDL-cholesterol decreased significantly (p<0.05) in all groups compared to the control. The activity of superoxide dismutase (SOD) reduced (p<0.05) significantly across all the groups and even after 36 hours of exposure. However, the activity of the glutathione peroxidase (GPx) was not affected following exposure to OP. The serum reduced glutathione (GSH) fell in a concentration dependent manner in all animals exposed to OP. Coumaphos exposure led to a significant (p<0.05) increase in serum MDA in a concentration dependent manner after 36 hours post exposure. The serum nitric oxide (NO) and MPO content increased (p<0.05) significantly following exposure to different concentrations of Coumaphos. The activity of Acetyl cholinesterase (AchE) fell significantly from the normal concentration of the OP down to the highest concentration. The activity of serum creatine phosphokinase (CK) increased (p<0.05) significantly in groups C and D compared to the control and recommended concentration. Electrocardiographic abnormalities recorded included low-voltage R-waves, first degree heart block, significant increased (p<0.05) heart rate (HR) and shortened QT interval compared to the control and recommended concentrations. Taking together, coumaphos poisoning caused an inhibition of AchE and significant potentially fatal arrhythmias via the induction of oxidative stress.

Keywords

Coumaphos, Organophosphate Poisoning (OP), Electrocardiogram (ECG), Oxidative Stress, Acetylcholinesterase (AchE), Cardiotoxicity.
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  • Van Brussel E, Ghuysen A. [Acute voluntary poisoning by carbamate]. Rev Med Liege 2014; 69(12):650-653.

  • Pankaj M, Krishna K. Acute organophosphorus poisoning complicated by acute coronary syndrome. J Assoc Physicians India 2014; 62(7):614-616.

  • Çolak Ş, Erdoğan MÖ, Baydin A, Afacan MA, Kati C, Duran L. Epidemiology of organophosphate intoxication and predictors of intermediate syndrome. Turk J Med Sci 2014;44(2):279-282.

  • Iyer R, Iken B, Leon A. Developments in alternative treatments for organophosphate poisoning. Toxicol Lett 2015; 233(2):200-206.

  • Jayawardane P, Senanayake N, Buckley NA, Dawson AH. Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: evidence for differential roles of muscarinic and nicotinic stimulation. Clin Toxicol (Phila) 2012; 50(4):250-253.

  • Repplinger D, Su MK, McKinnon K. Troponin elevations and organophosphate poisoning: direct cardiac injury or demand ischemia? Clin Toxicol (Phila) 2014; 52(10):1298.

  • Cha YS, Kim H, Go J, Kim TH, Kim OH, Cha KC, Lee KH, Hwang SO. Features of myocardial injury in severe organophosphate poisoning. Clin Toxicol (Phila) 2014; 52(8):873879.

  • Aghabiklooei A, Mostafazadeh B, Farzaneh E, Morteza A. Does organophosphate poisoning cause cardiac injury? Pak J Pharm Sci 2013; 26(6):1247-1250.

  • Gu EE, Can I, Kusumoto FM. Case report: an unusual heart rhythm associated with organophosphate poisoning. Cardiovasc Toxicol 2012;12(3):263-265.

  • Lionte C, Sorodoc L, Petriş O, Sorodoc V. [Electrocardiographic changes in acute organophosphate poisoning]. Rev Med Chir Soc Med Nat Iasi 2007; 111(4):906-911.

  • Demirag K, Cankayali I, Eris O, Moral AR, Pehlivan M. The comparison of therapeutic effects of atropine and pralidoxime on cardiac signs in rats with experimental organophosphate poisoning. Adv Ther 2005; 22(2):79-86.

  • Joshi P, Manoria P, Joseph D, Gandhi Z. Acute myocardial infarction: can it be a complication of acute organophosphorus compound poisoning? J Postgrad Med 2013; 59(2):142-144.

  • PHS (PUBLIC HEALTH SERVICE) (1996). Public health service policy on humane care and the use of laboratory animals. US Department of Health and Humane services, Washington, DC, pp. 99-158.

  • Gornal AG, Bardawill JC, David MM. Determination of serum proteins by means of Biuret reaction. J Biol Chem 1949; 177: 751-766.

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzeneinduced liver necrosis; protective role of GSH & evidence for 3, 4 bromobenzene oxide as the hepatotoxic metabolite. JB lippinocott 1994; 108-144.

  • Buetler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963: 61: 882-888.

  • Misra HP, Fridovich I. The role of superoxide anoin in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 217: 3170-3175.

  • Oyagbemi AA, Omobowale TO, Akinrinde AS, Saba AB, Ogunpolu BS, Daramola O. Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environ Toxicol 2015;30:1235-43.

  • Omobowale TO, Oyagbemi AA, Akinrinde AS, Saba AB, Daramola OT, Ogunpolu BS, Olopade JO. Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats. Environ Toxicol Pharmacol 2014; 37(3):12021211.

  • Varshney R, Kale RK. Effect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes Int J Biol 1990; 158: 773-741

  • Wolff SP. Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol 1994; 233: 182-189.

  • Olaleye SB, Adaramoye OA, Erigbali PP, Adeniyi OS. Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats. World J Gastroenterol 2007; 13: 5121-5126.

  • Xia Y, Zweier JL. Measurement of myeloperoxidase in leukocytecontaining tissues. Anal Biochem 1997; 245: 93-96.

  • Whittaker M. Cholineterases. Bergmeyer, H. U. (Ed.). In Methods of Enzymatic

  • Analysis. (3rd ed.) Verlag Chemie, Weinheim, 1984; 52-63.

  • Alp H, Aytekin I, Hatipoglu NK, Alp A, Ogun M. Effects of sulforophane and curcumin on oxidative stress created by acute malathion toxicity in rats. Eur Rev Med Pharmacol Sci 2012 ;16 S3:144-148.

  • Kazi A, Oommen A. Monocrotophos induced oxidative damage associates with severe acetylcholinesterase inhibition in rat brain. Neurotoxicology 2012; 33(2):156-161.

  • Yang CC, Deng JF. Intermediate syndrome following organophosphate insecticide poisoning. J Chin Med Assoc 2007; 70(11):467-472.

  • Yurumez Y, Durukan P, Yavuz Y, Ikizceli I, Avsarogullari L, Ozkan S, Akdur O, Ozdemir C. Acute organophosphate poisoning in university hospital emergency room patients. Intern Med 2007; 46:965–969.

  • Bicker W, Lammerhofer M, Genser D, Kiss H, Lindner W. A case study of acute human chlorpyrifos poisoning: Novel aspects on metabolism and toxicokinetics derived from liquid chromatography-tandem mass spectrometry analysis of urine samples. Toxicol Lett 2005; 159:235–251.

  • Ozkan U, Osun A, Basarslan K, Senol S, Kaplan I, Alp H. Effects of intralipid and caffeic acid phenethyl ester on neurotoxicity, oxidative stress, and acetylcholinesterase activity in acute chlorpyriphos intoxication. Int J Clin Exp Med 2014; 7(4):837-846.

  • Zunec S, Kopjar N, Zeljezić D, Kuca K, Musilek K, Lucić Vrdoljak A. In vivo evaluation of cholinesterase activity, oxidative stress markers, cyto- and genotoxicity of K048 oxime–a promising antidote against organophosphate poisoning. Basic Clin Pharmacol Toxicol 2014; 114(4):344-351.

  • Lukaszewicz-Hussain A. Role of oxidative stress in organophosphate insecticide toxicity - Short review. Pesticide Biochem Physiol 2010; 98:145-150.

  • Oliveira OM, Brunetti IL, Khalil NM. Nicotine-enhanced oxidation of low-density lipoprotein and its components by myeloperoxidase/H2O2/Cl- system. An Acad Bras Cienc 2015; 87(1):183-192.

  • Cynshi O, Tamura K, Niki E.Design, synthesis, and action of antiatherogenic antioxidants. Methods Mol Biol 2010; 610:91-107.

  • de Lima Portella R, Barcelos RP, de Bem AF, Carratu VS, Bresolin L, da Rocha JB, Soares FA. Oximes as inhibitors of low density lipoprotein oxidation. Life Sci 2008; 83(2526):878-885.

  • Cynshi O, Stocker R.Inhibition of lipoprotein lipid oxidation. Handb Exp Pharmacol 2005; (170):563-590.

  • Matos A, da Silva AP, Gil Â, Beatriz C, Portelinha A, Rebelo I, Areias MJ, Bicho M. Myeloperoxidase and endothelial nitric oxide synthase genetic polymorphisms and its modulation of some cardiovascular risk parameters in women with previous pregnancy hypertension. Pregnancy Hypertens 2015; 5(1):38.

  • Morgan PE, Laura RP, Maki RA, Reynolds WF, Davies MJ. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase. Free Radic Res 2015; 27:1-7.

  • Ryhänen R, Herranen J, Korhonen K, Penttilä I, Polvilampi M, Puhakainen E.Relationship between serum lipids, lipoproteins and pseudocholinesterase during organophosphate poisoning in rabbits. Int J Biochem 1984; 16(6):687690.

  • Zhang JW, Lv GC, Zhao Y. The significance of the measurement of serum xanthine oxidase and oxidation markers in patients with acute organophosphorus pesticide poisoning. J Int Med Res 2010; 38(2):458-465

  • Mishra V, Srivastava N.Organophosphate pesticides-induced changes in the redox status of rat tissues and protective effects of antioxidant vitamins. Environ Toxicol 2015; 30(4):472-482.

  • Hundekari IA, Suryakar AN, Rathi DB.Acute organo-phosphorus pesticide poisoning in North Karnataka, India: oxidative damage, haemoglobin level and total leukocyte. Afr Health Sci 2013; 13(1):129-136.

  • Shafiee H, Mohammadi H, Rezayat SM, Hosseini A, Baeeri M, Hassani S, Mohammadirad A, Bayrami Z, Abdollahi M.Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle. Toxicol Mech Methods 2010; 20(9):538-543

  • Wanf ZX, Wang CX, Liu SH, Shi JH, Tu YY.[Variation and clinical significance of serum CTnT and CK-MB in patients with acute organophosphorus pesticid poisoning].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011; 27(1):90-91

  • Atale N, Gupta K, Rani V.Protective effect of Syzygium cumini against pesticide-induced cardiotoxicity. Environ Sci Pollut Res Int 2014; 21(13):7956-7972.

  • Mohammadi H, Karimi G, Seyed Mahdi Rezayat, Ahmad Reza Dehpour, Shafiee H, Nikfar S, Baeeri M, Sabzevari O, Abdollahi M. Benefit of nanocarrier of magnetic magnesium in rat malathion-induced toxicity and cardiac failure using non-invasive monitoring of electrocardiogram and blood pressure. Toxicol Ind Health 2011; 27(5):417-429.

  • Aghabiklooei A, Mostafazadeh B, Farzaneh E, Morteza A. Does organophosphate poisoning cause cardiac injury? Pak J Pharm Sci 2013; 26(6):1247-1250.

  • Mollace V, Gliozzi M, Musolino V, Carresi C, Muscoli S, Mollace R, Tavernese A, Gratteri S, Palma E, Morabito C, Vitale C, Muscoli C, Fini M, Romeo F. Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells: Role of oxidative stress and LOX-1 receptor expression.Int J Cardiol 2015; 184C:152-158.

  • Aydin MU, Aygul N, Altunkeser BB, Unlu A, Taner A.Comparative effects of high-dose atorvastatin versus moderatedose rosuvastatin on lipid parameters, oxidized-LDL and inflammatory markers in ST elevation myocardial infarction. Atherosclerosis 2015; 239(2):439-443.

  • Kim CH, Mitchell JB, Bursill CA, Sowers AL, Thetford A, Cook JA, van Reyk DM, Davies MJ.The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE-/- mice. Atherosclerosis 2015; 240(1):234-241.

  • Lubrano V, Balzan S. Consolidated and emerging inflammatory markers in coronary artery disease. World J Exp Med 2015; 5(1):21-32.

  • Stankovic S, Majkic-Singh N.Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors. Crit Rev Clin Lab Sci 2010 47(2):72-123.

  • Karki P, Ansari JA, Bhandary S, Koirala S. Cardiac and electrocardiographical manifestations of acute organophosphate poisoning. Singapore Med J 2004 45(8):385-9.

  • Anand S1, Singh S, Nahar Saikia U, Bhalla A, Paul Sharma Y, Singh D.Cardiac abnormalities in acute organophosphate poisoning.Clin Toxicol (Phila). 2009; 47(3):230-5.

  • Patel C, Yan GX, Antzelevitch C. Short QT syndrome: from bench to bedside. Circ Arrhythm Electrophysiol 2010 3(4):401-8.

  • Laudari S, Patowary BS, Sharma SK, Dhungel S, Subedi K, Bhattacharya R, et al. Cardiovascular Effects of Acute Organophosphate Poisoning. Asia Pacific Journal of Medical Toxicology 2014;3(2):65-9.

  • Senthilkumaran S, Balamurugan N, Jayaraman S, Thirumalaikolundusubramaniam P.Cardiotoxicity in OPC poisoning: Time to think differential diagnosis. J Postgrad Med. 2013; 59(4):337.

  • Karasu-Minareci E1, Gunay N, Minareci K, Sadan G, Ozbey G.What may be happen after an organophosphate exposure: acute myocardial infarction? J Forensic Leg Med. 2012; 19(2):94-6.


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  • Concentration-Dependent Inhibition of Acetylcholinesterase by Organophosphate Poisoning in Dogs: A Biochemical and Electrocardiograph Study

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Authors

O. E. Ola-Davies
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
A. A. Oyagbemi
Department of Veterinary Physiology, Biochemistry and Pharmacology, University of Ibadan, Nigeria
T. O. Omobowale
Department of Veterinary Medicine, University of Ibadan, Nigeria

Abstract


Organophosphate poisoning (OP) is one of the most common poisonings in developing countries. In this study, twentyfour dogs in four groups of six each were used. Control group bathed with water only, group B with 16% Coumaphos (recommended), groups C and D with times 10 and 20 of 16% Coumaphos, respectively. Blood was collected from cephalic vein for biochemical assays. Electrocardiographic parameters were assessed from a Lead-II electrocardiogram. There was a significant increase (p<0.05) in total cholesterol in group B and D compared to the control. LDL-cholesterol decreased significantly (p<0.05) in all groups compared to the control. The activity of superoxide dismutase (SOD) reduced (p<0.05) significantly across all the groups and even after 36 hours of exposure. However, the activity of the glutathione peroxidase (GPx) was not affected following exposure to OP. The serum reduced glutathione (GSH) fell in a concentration dependent manner in all animals exposed to OP. Coumaphos exposure led to a significant (p<0.05) increase in serum MDA in a concentration dependent manner after 36 hours post exposure. The serum nitric oxide (NO) and MPO content increased (p<0.05) significantly following exposure to different concentrations of Coumaphos. The activity of Acetyl cholinesterase (AchE) fell significantly from the normal concentration of the OP down to the highest concentration. The activity of serum creatine phosphokinase (CK) increased (p<0.05) significantly in groups C and D compared to the control and recommended concentration. Electrocardiographic abnormalities recorded included low-voltage R-waves, first degree heart block, significant increased (p<0.05) heart rate (HR) and shortened QT interval compared to the control and recommended concentrations. Taking together, coumaphos poisoning caused an inhibition of AchE and significant potentially fatal arrhythmias via the induction of oxidative stress.

Keywords


Coumaphos, Organophosphate Poisoning (OP), Electrocardiogram (ECG), Oxidative Stress, Acetylcholinesterase (AchE), Cardiotoxicity.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi1%2F146672