Protective Effect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats
Novelty in Biomedicine,
Vol. 5 No. 3 (2017),
11 June 2017
AbstractBackground: The negative consequence of methamphetamine abuse is due to neuropathologic changes in the brain, which reduces dopaminergic neurons and result in damage to different brain areas. Neurotoxicity induced by methamphetamine increases the oxidative stress and associated with neuronal apoptosis. The role of the antioxidant coenzyme Q10 probably produces its neuroprotective effects. Therefore, the purpose of the present study was to examine the protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats.
Materials and Methods: Fifty Wistar eight-week adult rats randomly divided into 5 groups: Healthy control, methamphetamine injection (Meth), methamphetamine injection and CoQ10 5mg/kg treatment (Meth+Post CoQ10 5mg/kg), methamphetamine injection and CoQ10 10mg/kg treatment (Meth+Post CoQ10 10mg/kg), methamphetamine injection and CoQ10 20mg/kg treatment (Meth+Post CoQ10 20mg/kg). Methamphetamine with a purity of 96% with a dosage of 20 mg/kg was injected Intraperitoneal. Coenzyme Q10 for three treatment groups was injected intraperitoneally for 14 days in a dosage of 5, 10 and 20 mg/kg/day. The protein expressions of Baxand Bcl2 were evaluated by western blotting technique.
Results: Bax protein expression was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.010) and so Meth+Post CoQ10 10mg/kg (p=0.004) comparing to Meth group. In addition, Bcl2 protein expression was significantly higher in Meth+Post CoQ10 5mg/kg comparing to Meth group (p=0.018). However, there were no significant differences between control and CoQ10 treatment groups. Bax/Bcl2 ratio was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.005), Meth+Post CoQ10 10mg/kg (p=0.008) and Meth+Post CoQ10 20mg/kg (p=0.044) comparing to Meth group.
Conclusion: We suggest that CoQ10 reduces the methamphetamine-induced apoptosis in the striatum of the rats through the reduction of apoptotic factors and increase of anti-apoptotic pathways.
- Coenzyme Q10
How to Cite
Golmirzaei J, Amiri S, Rastikerdar N, Mozaffari J, Sadeghi P, Mahboobi HR, Khorgoei T. Prevalence and risk factors of methamphetamine use among high school students of Bandar Abbas. International Electronic Journal of Medicine (IEJM) . 2014;3(1): 39-46.
United Nations Office on Drugs and Crime.World drug report volume 1. Analysis.United Nations Publication.2005, Sales No. E.05.XI.10.
Krasnova IN, Cadet JL.Methamphetamine toxicity and messengers of death. Brain Res Rev. 2009;60(2):379-407.
Homer BD, Solomon TM, Moeller RW, Mascia A, DeRaleau L, Halkitis PN. Methamphetamine abuse and impairment of social functioning: a review of the underlying neurophysiological causes and behavioral implications.Psychol Bull. 2008;134(2):301-10.
Darke S, Kaye S, McKetin R, Duflou J. Major physical and psychological harms of methamphetamine use. Drug Alcohol Rev. 2008;27(3):253-62.
Kita T, Wagner GC, Nakashima T. Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption. J Pharmacol Sci. 2003;92(3):178-95.
Riddle EL, Fleckenstein AE, Hanson GR. Mechanisms of methamphetamine-induced dopaminergic neurotoxicity. AAPS J. 2006;8(2):E413-8.
McCann UD, Kuwabara H, Kumar A, Palermo M, Abbey R, Brasic J, Ye W, Alexander M, Dannals RF, Wong DF, Ricaurte GA. Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users. Synapse. 2008;62(2):91-100.
Sekine Y, Ouchi Y, Sugihara G, Takei N, Yoshikawa E, Nakamura K, Iwata Y, Tsuchiya KJ, Suda S, Suzuki K, Kawai M, Takebayashi K, Yamamoto S, Matsuzaki H, Ueki T, Mori N, Gold MS, Cadet JL. Methamphetamine causes microglial activation in the brains of human abusers. J Neurosci. 2008;28(22):5756-61.
Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED. Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci. 2004;24(26):6028-36.
Kuczenski R, Everall IP, Crews L, Adame A, Grant I, Masliah E. Escalating dose-multiple binge methamphetamine exposure results in degeneration of the neocortex and limbic system in the rat. Exp Neurol. 2007;207:42–51.
Chou J, Luo Y, Kuo CC, Powers K, Shen H, Harvey BK, Hoffer BJ, Wang Y. Bone morphogenetic protein-7 reduces toxicity induced by high doses of methamphetamine in rodents. Neuroscience. 2008;151(1):92-103.
Stephans SE, Yamamoto BK. Methamphetamine-induced neurotoxicity: roles for glutamate and dopamine efflux. Synapse. 1994;17(3):203-9.
Michel PP, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res. 1990;26(4):428-35.
Wu CW, Ping YH, Yen JC, Chang CY, Wang SF, Yeh CL, Chi CW, Lee HC. Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis. Toxicol Appl Pharmacol. 2007;220(3):243-51.
Potula R, Hawkins BJ, Cenna JM, Fan S, Dykstra H, Ramirez SH, Morsey B, Brodie MR, PersidskyY.Methamphetamine causes mitrochondrial oxidative damage in human T lymphocytes leading to functional impairment.JImmunol. 2010;185(5):2867-76.
Oliveira MT, Rego AC, Morgadinho MT, Macedo TRA, OlivieiraCR .Toxic effects of opioid and stimulant drugs on undifferentiated PC12 cells.Ann NY Acad Sci. 2002; 965:487–496.
Gold MS, Kobeissy FH, Wang KK, Merlo LJ, Bruijnzeel AW, Krasnova IN, Cadet JL. Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry. 2009;66(2):118-27.
Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. BiochimBiophysActa. 2004;1660(1-2):171-99.
Thrash B, Karuppagounder SS, Uthayathas S, Suppiramaniam V, Dhanasekaran M. Neurotoxic effects of methamphetamine. Neurochem Res. 2010;35(1):171-9.
Somayajulu M, McCarthy S, Hung M, Sikorska M, Borowy-Borowski H, Pandey S. Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10. Neurobiol Dis. 2005;18(3):618-27.
Shults CW. Therapeutic role of coenzyme Q(10) in Parkinson's disease. PharmacolTher. 2005;107(1):120-30.
Klongpanichapak S, Govitrapong P, Sharma SK, EbadiM.Attenuation of cocaine and methamphetamine neurotoxicity by coenzyme Q10.Neurochem Res. 2006;31(3):303-11.
Salamone JD. Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. Psychopharmacology (Berl). 1992;107(2-3):160-74.
Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, Grant I. Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol. Rev. 2007;17:275–297.
Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease.Annu Rev Neurosci.1999; 22:123–144.
Deng X, Wang Y, Chou J, Cadet JL. Methamphetamine causes widespread apoptosis in the mouse brain: evidence from using an improved TUNEL histochemical method. Brain Res Mol Brain Res. 2001;93(1):64-9.
Cadet JL, Krasnova IN. Molecular bases of methamphetamine-induced neurodegeneration. Int Rev Neurobiol. 2009;88:101-19.
Ebadi M, Brown-Borg H, Garrett S, Singh B, Shavali S, Sharma S .Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson’s disease. Mol Brain Res. 2005;134:67–75.
Moon Y, Lee KH, Park JH, Geum D, Kim K. Mitochondrial membrane depolarization and the selective death of dopaminergic neurons by rotenone: protective effect of coenzyme Q10. J Neurochem. 2005;93(5):1199-208.
Echtay KS, Winkler E, Klingenberg M. Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature. 2000;408(6812):609-13.
Alleva R, Tomasetti M, Andera L, Gellert N, Borghi B, Weber C, Murphy MP, Neuzil J. Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection. FEBS Lett. 2001;503(1):46-50.
Naderi J, Somayajulu-Nitu M, Mukerji A, Sharda P, Sikorska M, Borowy-Borowski H, Antonsson B, Pandey S. Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells. Apoptosis. 2006;11(8):1359-69.
Tomasetti M, Alleva R, Borghi B, Collins AR. In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage. FASEB J. 2001;15(8):1425-7.
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