Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity

Document Type : Original Article

Authors

1 Department of Toxicology, Faculty of Pharmacy, Islamic Azad University, Shahreza Branch, Shahreza, Iran

2 Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

4 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pathology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

6 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

7 Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.
Materials and Methods: Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.
Results: ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (P<0.05). ILE reduced freezing and stereotyped behaviors and increased rearing responses (P<0.05). Locomotor activity also returned to control levels especially during the last hours of the experiment. ILE administration decreased the prevalence of pulmonary emphysema in the lungs (PP<0.01) and percentages of TUNEL positive cells in the brain (P<0.05), in comparison with the control group.
Conclusion: ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.

Keywords


1. Courtney KE, Ray LA. Methamphetamine: an update on epidemiology, pharmacology, clinical phenomeno-logy, and treatment literature. Drug Alcohol Depend 2014; 143: 11-21.
2. Cadet JL, Krasnova IN, Jayanthi S, Lyles J. Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 2007; 11: 183-202.
3. Kiyatkin EA, Sharma HS. Acute methamphetamine intoxication: brain hyperthermia, blood-brain barrier, brain edema, and morphological cell abnormalities. Int Rev Neurobiol 2009; 88: 65-100.
4. Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction 2009; 104: 1085-99.
5. Davis GG, Swalwell CI. The incidence of acute cocaine or methamphetamine intoxication in deaths due to ruptured cerebral (berry) aneurysms. J Forensic Sci 1996; 41: 626-8.
6. Jang DH, Amphetamine. In, Hoffman RS, et al, Editors. Goldfrank's Toxicologic Emergencies. McGraw-Hill Professional: New York 2015 p. 1029-1037.
7. Hallberg D, Holm I, Obel AL, Schuberth O, Wretlind A. Fat emulsions for complete intravenous nutrition. Postgrad Med J 1967; 43: 307-16.
8. Zhao M, Su M, Lin X, Luo Y, He H, Cai C, et al. Evaluation of docetaxel-loaded intravenous lipid emulsion: pharmacokinetics, tissue distribution, antitumor activity, safety and toxicity. Pharm Res 2010; 27:1687-702.
9. Hippalgaonkar K,Majumdar S,Kansara V. Injectable lipid emulsions-advancements, opportunities and challenges. AAPS PharmSciTech 2010; 11:1526-40.
10. Patlolla RR, Vobalaboina V. Pharmacokinetics and tissue distribution of etoposide delivered in parenteral emulsion. J Pharm Sci 2005; 94: 437-45.
11. Bania  TC, Antidotes in Depth, intravenous fat emulsion. In, Hoffman R S, et al, Editors. Goldfrank's Toxicologic Emergencies. McGraw-Hill Professional: New York.2015 p. 976-710.
12. Moshiri M, Vahabzadeh M, Mohammadpour A H, Hosseinzadeh H. Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbits. Toxicol Ind Health 2016; 945-952.
13. Vahabzadeh M, Moshiri M, Mohammadpour A H, Hosseinzadeh H. Promising effects of intravenous lipid emulsion as an antidote in acute tramadol poisoning. Reg Anesth Pain Med 2013; 38:425-430.
14. Perez E, Bania T C, Medlej K, Chu J. Determining the optimal dose of intravenous fat emulsion for the treatment of severe verapamil toxicity in a rodent model. Academic emergency medicine 2008; 15: 1284-1289.
15. Sanberg PR, Zoloty SA, Willis R, Ticarich CD, Rhoads K, Nagy RP, et al. Digiscan activity: automated measurement of thigmotactic and stereotypic behavior in rats. Pharmacol Biochem Behav 1987; 27:569-72.
16. Etemad L, Jafarian AH, Moallem SA. Pathogenesis of Pregabalin-Induced Limb Defects in Mouse Embryos. J Pharm Pharm Sci 2015; 18:882-889.
17. Ciechanowicz S,Patil V. Lipid emulsion for local anesthetic systemic toxicity. Anesthesiol Res Pract 2012; 2012:1-11.
18. Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med 2010; 18: 51.
19. Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity. Acad Emerg Med 2006; 13: 134-139.
20. Moshiri M, Vahabzadeh M, Etemad L, Hosseinzadeh H. Failure of Intravenous Lipid Emulsion to Reduce Diazinon-induced Acute Toxicity: a Pilot Study in Rats. Iran J Pharm Res 2013; 12:897-902.
21. Yoav G, Odelia G, Shaltiel C. A lipid emulsion reduces mortality from clomipramine overdose in rats. Vet Hum Toxicol 2002; 44:30.
22. Moshiri M, Mohammadpour AH, Vahabzadeh M, Etemad L, Memar B, Hosseinzadeh H. Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit. BioMed Res Inter 2014; 2014:1-9.
23. Arora NP, Berk WA, Aaron CK, Williams KA. Usefulness of intravenous lipid emulsion for cardiac toxicity from cocaine overdose. Am J Cardiol 2013; 111: 445-447.
24. Weinberg G, Lin B, Zheng S, Di Gregorio G, Hiller D, Ripper R, et al. Partitioning effect in lipid resuscitation: further evidence for the lipid sink. Crit Care Med 2010; 38: 2268-2269.
25. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol (Phila) 2011; 49: 801-809.
26. Harris DS, Boxenbaum H, Everhart ET, Sequeira G, Mendelson JE, Jones RT. The bioavailability of intranasal and smoked methamphetamine. Clin Pharmacol Ther 2003; 74:475-486.
27. Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, et al. Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 1993; 21:717-723.
28. Randrup A, Munkvad I, Udsen P. Adrenergic Mechanisms and Amphetamine Induced Abnormal Behaviour. Acta Pharmacol Toxicol (Copenh) 1963; 20: 145-157.
29. Harvey MG, Cave GR. Intralipid infusion ameliorates propranolol-induced hypotension in rabbits. J Med Toxicol 2008; 4:71-76.
30. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998; 88:1071-1075.
31. Calenda E, Dinescu SA. Failure of lipid emulsion to reverse neurotoxicity after an ultrasound-guided axillary block with ropivacaine and mepivacaine. J Anesth 2009; 23:472-3.
32. Zimmer C, Piepenbrink K, Riest G, Peters J. Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion. Anaesthesist 2007; 56:449-453.
33. Jakkala-Saibaba R, Morgan PG, Morton GL. Treatment of cocaine overdose with lipid emulsion. Anaesthesia 2011; 66: 168-1170.
34. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, et al. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine. Ann Emerg Med 2008; 51:412-415.
35. Tse J, Ferguson K, Whitlow KS, Erickson K. The use of intravenous lipid emulsion therapy in acute methamphetamine toxicity. Am J Emerg Med 2015; 1732.e3–1732.e4.
36. Derlet RW, Rice P, Horowitz BZ, Lord RV. Amphetamine toxicity: experience with 127 cases. J Emerg Med 1989; 7:157-161.
37. Inoue H, Ikeda N, Kudo K, Ishida T, Terada M, Matoba R. Methamphetamine-related sudden death with a concentration which was of a 'toxic level'. Leg Med (Tokyo) 2006; 8:150-155.
38. Levine M, Sholnik AB, Ruha AM, Bosak A, Menke N, Pizon AF. Complication  following antidotial use of  intravenous lipid emulsion therapy. J Med Toxicol 2014; 10:10-14.
39. Karpe F, Olivecrona T, Olivecrona G, Samra JS, Summers LK, Humphreys SM, et al. Lipoprotein lipase transport in plasma: role of muscle and adipose tissues in regulation of plasma lipoprotein lipase concentrations. J Lipid Res 1998; 39:2387-93.
40. Peterson J, Bihain BE, Bengtsson-Olivecrona G, Deckelbaum RJ, Carpentier YA, Olivecrona T. Fatty acid control of lipoprotein lipase: a link between energy metabolism and lipid transport. Proc Natl Acad Sci USA 1990; 87:909-913.
41. Sloboda N, Feve B, Thornton SN, Nzietchueng R, Regnault V, Simon G, et al. Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucker rats. J Gerontol A Biol Sci Med Sci 2012; 67:927-38.
42. Venus B, Prager R, Patel CB, Sandoval E, Sloan P, Smith RA. Cardiopulmonary effects of Intralipid infusion in critically ill patients. Crit Care Med 1988; 16:587-590.
43. Hwang TL, Huang SL, Chen MF. Effects of intravenous fat emulsion on respiratory failure. Chest 1990; 97:934-938.
44. Lekka ME, Liokatis S, Nathanail C, Galani V, Nakos G. The impact of intravenous fat emulsion administration in acute lung injury. Am J Respir Crit Care Med 2004; 169: 638-644.
45. Qiao D, Xu J, Le C, Huang E, Liu C, Qiu P, et al. Insulin-like growth factor binding protein 5 (IGFBP5) mediates methamphetamine-induced dopaminergic neuron apoptosis. Toxicol Lett 2014; 230: 444-453.