he effects of vitamin B12 on the brain damages caused by methamphetamine in mice

Document Type: Original Article

Authors

1 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

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

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

4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Ahl Al Bayt, Karbala, Iraq

5 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

7 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

8 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Methamphetamine (METH) is a powerful stimulant drug that directly affects the brain and induces neurological deficits. B12 is a water-soluble vitamin (vit) that is reported to attenuate neuronal degeneration. The goal of the present study is to investigate the effect of vitamin B12 on METH’s neurodegenerative changes.
Materials and Methods: Two groups of 6 animals received METH (10 mg/kg, interaperitoneally (IP)) four times with a 2 hr interval. Thirty mins before METH administration, vit B12 (1 mg/kg) or normal saline were injected IP. Animals were sacrificed 3 days after the last administration. Caspase proteins levels were measured by Western blotting. Also, samples were examined by TUNEL assay to detect the presence of DNA fragmentation. Reduced glutathione (GSH) was also determined by the Ellman method.
Results: The pathological findings showed that vit B12 attenuates the gliosis induced by METH. Vit B12 administration also significantly decreased the apoptotic index in the striatum and the cerebral cortex (P<0.001). It also reduced caspase markers compared to the control (PConclusion: The current study suggests that parenteral vit B12 at safe doses may be a promising treatment for METH-induced brain damage via inhibition of  neuron apoptosis and increasing the reduced GSH level. Research focusing on the mechanisms involved in the protective responses of vit B12 can be helpful in providing a novel therapeutic agent against METH-induced neurotoxicity.

Keywords

Main Subjects


1. Cadet JL, Krasnova IN, Jayanthi S, Lyles J. Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 2007; 11: 183-202.
2. Chulathidaa C, Summon C. Global patterns of methamphetamine use. Curr Opin Psychiatry 2015; 28 269-274.
3.    Kishi T, Ikeda M, Kitajima T, Yamanouchi Y, Kinoshita Y, Kawashima K, et al. Prostate apoptosis response 4 gene is not associated with methamphetamine-use disorder in the Japanese population. Ann N Y Acad Sci 2008; 1139: 83-88.
4.    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.
5.    Rusyniak DE. Neurologic manifestations of chronic methamphetamine abuse. Neurol Clin 2011; 29: 641-655.
6.    Karch SB, Karchs Pathology of Drug Abuse. 3rd ed. 2001. Boca Raton (FL): CRC Press.
7.    Martin WR, Sloan JW, Sapira JD, Jasinski DR. Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 1971; 12: 245-258.
8.    Rothman RB, Baumann MH. Monoamine transporters and psychostimulant drugs. Eur J Pharmacol 2003; 479: 23-40.
9.    Ladenheim B, Krasnova IN, Deng X, Oyler JM, Polettini A, Moran TH, et al. Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Mol Pharmacol 2000; 58: 1247-1256.
10.    Barayuga SM, Pang X, Andres MA, Panee J, Bellinger FP. Methamphetamine decreases levels of glutathione peroxidases 1 and 4 in SH-SY5Y neuronal cells: protective effects of selenium. Neurotoxicology 2013; 37: 240-246.
11. Ghadiri  A, Etemad L, Moshiri M, Moallem SA, Jafarian AH, Hadizadeh F and M, et al. Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity. IJBMS, 2017;20: 138-144.
12.    Hosseinzadeh H, Taiari S, Nassiri-Asl M. Effect of thymoquinone, a constituent of Nigella sativa L., on ischemia-reperfusion in rat skeletal muscle. Naunyn Schmiedebergs Arch Pharmacol 2012; 385: 503-508.
13.    Carr DF, Whiteley G, Alfirevic A, Pirmohamed M, Fol A st. Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review. Pharmacogenomics J 2009; 9: 291-305.
14.    Scalabrino G, Corsi MM, Veber D, Buccellato FR, Pravettoni G, Manfridi A, et al. Cobalamin (vitamin B(12)) positively regulates interleukin-6 levels in rat cerebrospinal fluid. J Neuroimmunol 2002; 127: 37-43.
15.    Zhu JP, Xu W, Angulo N, Angulo JA. Methamphetamine-induced striatal apoptosis in the mouse brain: comparison of a binge to an acute bolus drug administration. Neurotoxicology 2006; 27: 131-136.
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. Bigdeli L, Asia MN, Miladi-Gorji H, Fadaei A. The spatial learning and memory performance in methamphetamine-sensitized and withdrawn rats. IJBMS 2015; 18: 234-239.
18.    Deng X, Cai NS, McCoy MT, Chen W, Trush MA, Cadet JL. Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway. Neuropharmacology 2002; 42: 837-845.
19.    Tong J, Fitzmaurice P, Furukawa Y, Schmunk GA, Wickham DJ, Ang lC, et al. Is brain gliosis a characteristic of chronic methamphetamine use in the human?. Neurobiology of Disease 2014; 67: 107-118.
20.    Karimi A, Parivar K, Nabiuni M, Haghighi S, Imani S. Effect of honey bee venom and vitamin B12 on gliosis of brain stem in rats with experimental allergic encephalomyelitis-animal model for multiple sclerosis. Journal of cell & tissue 2011; 1: 37-45.
21.    Hosseinzadeh H, Moallem SA, Moshiri M, Sarnavazi M S, Etemad L. Anti-nociceptive and Anti-infl ammatory Effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice. Arzneimittelforschung 2012; 62: 324-329.
22.    Lalonde R, Barraud H, Ravey J, Gueant JL, Bronowicki JP, Strazielle C. Effects of a B-vitamin-deficient diet on exploratory activity, motor coordination, and spatial learning in young adult BALB/c mice. Brain Res 2008; 1188: 122-131.
23.    Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6.
24.    Tokunaga I, Ishigami A, Kubo S, Gotohda T, Kitamura O. The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain. J Med Invest 2008; 55: 241-245.
25.    Eisch AJ, Marshall JF. Methamphetamine neurotoxicity: dissociation of striatal dopamine terminal damage from parietal cortical cell body injury. Synapse 1998; 30: 433-445.
26.    Halpin LE, Collins SA, Yamamoto BK. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sci 2014; 97: 37-44.
27.    Jayanthi S, Deng X, Bordelon M, McCoy MT, Cadet JL. Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex. FASEB J 2001; 15: 1745-52.
28.    Tamaddonfard E, Farshid AA, Samadi F, Eghdami K. Effect
of vitamin B12 on functional recovery and histopathologic changes of tibial nerve-crushed rats. Drug Res (Stuttg) 2014; 64:470-475.
29.    Hobbenaghi R, Javanbakht J, Hosseini E, Mohammadi S, Rajabian M, Moayeri P, et al. Neuropathological and neuroprotective features of vitamin B12 on the dorsal spinal ganglion of rats after the experimental crush of sciatic nerve: an experimental study. Diagn Pathol 2013; 8: 123.
30.    Harold C, Wallace T, Friedman R, Gudelsky G, Yamamoto B. Methamphetamine selectively alters brain glutathione. Eur J Pharmacol 2000; 400: 99-102.
31.    Mirecki A, Fitzmaurice P, Ang L, Kalasinsky KS, Peretti FJ, Aiken SS, et al. Brain antioxidant systems in human methamphetamine users. J Neurochem 2004; 89: 1396-1408.
32.    Kousik SM, Graves SM, Napier TC, Zhao C, Carvey PM. Methamphetamine-induced vascular changes lead to striatal hypoxia and dopamine reduction. Neuroreport 2011; 22: 923-928.
33.    Manzanares W, Hardy G. Vitamin B12: the forgotten micronutrient for critical care. Curr Opin Clin Nutr Metab Care 2010; 13: 662-668.
34.    Wheatley C. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock. Med Hypotheses 2006; 67: 124-142.