The Effect of Chronic Administration of Amphetamine-Type Stimulants on Oxidative Stress and Inflammation in Wistar Rats

Authors

  • Vita Camellia Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia & Department of Psychiatry, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia. https://orcid.org/0000-0001-5774-3276
  • Fasihah Irfani Fitri Department of Neurology, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia. https://orcid.org/0000-0002-0883-3029
  • Muhammad Ichwan Department of Pharmacology & Therapeutic, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia. https://orcid.org/0000-0001-8380-9099
  • Dina Keumala Sari Department of Nutrition, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia.
  • Elmeida Effendy Department of Psychiatry, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia.
  • Aldy Safruddin Rambe Department of Neurology, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia.
  • Syafruddin Ilyas Faculty of Biology, Universitas Sumatra Utara, Medan, Indonesia.
  • Juliandi Department of Public Health, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia. https://orcid.org/0000-0002-1090-2003
  • Alfi Khatib Faculty of Pharmacy, International Islamic University Malaysia, Kuala Lumpur, Malaysia.
  • Mustafa Mahmud Amin Department of Psychiatry, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia.
  • Muhammad Rusda Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatra Utara, Medan, Indonesia. https://orcid.org/0000-0002-2268-6838

DOI:

https://doi.org/10.21123/bsj.2023.9170

Keywords:

amphetamine-type stimulants, glutathione peroxidase, IL-6, inflammation, oxidative stress, tumor necrosis factor-α

Abstract

This study aims to determine the effect of chronic administration of amphetamine-type stimulants at varying doses on inflammation and oxidative stress in Wistar rats. They were given methylphenidate and divided into 4 treatment groups. Furthermore, simple random grouping was carried out to divide the samples into 5 groups, each consisting of 9 rats. These groups included rats given only distilled water as the controls, as well as those given methylphenidate at doses of 10 mg/kg BW, 20 mg/kg BW, and 40 mg/kg BW for 4 weeks as the experimental groups. Statistical analysis was then performed using GraphPad Prism to compare the effects of oxidative stress, systemic inflammation, BDNF, and spatial memory of the Wistar rats. Chronic administration of stimulants led to a significant decrease in glutathione peroxidase levels as well as an increase in the release of IL-6 and tumor necrosis factor-α compared to the control group. Based on the results, the pathways involved in cognitive impairment, which were related to the use of amphetamine-type stimulants played a role in addressing the detrimental effect of substance abuse and their comorbidities

References

United Nations Office on Drugs and Crime. The Challenge Of Synthetic Drugs In East And South-East Asia, Trends And Patterns Of Amphetamine-Type Stimulants Ad New Psychoactive Substances. 2017. https://www.unodc.org/roseap/uploads/documents/Publications/2022/Synthetic_Drugs_in_East_and_Southeast_Asia_2022_web.pdf

Boland R, Verduin M, Ruiz P. Kaplan & Sadock’s Synopsis of Psychiatry. 12th ed. Lippincott Williams & Wilkins (LWW); 2021.

Camellia V, Fitri FI, Husada MS, Aldiansyah D, Ichwan M, Khairunnisa K, et al. Sociological and Psychological Factors on Prohibited Substances Abuse in Rehabilitation Centre of Medan City, Indonesia. Open Access Maced J Med Sci. 2019; 7: 4137–4142. https://doi.org/10.3889/oamjms.2019.611.

Yang X, Wang Y, Li Q, Zhong Y, Chen L, Du Y, et al. The Main Molecular Mechanisms Underlying Methamphetamine- Induced Neurotoxicity and Implications for Pharmacological Treatment. Front Mol Neurosci. 2018; 11: 186. https://doi.org/10.3389/fnmol.2018.00186.

Moratalla R, Khairnar A, Simola N, Granado N, García-Montes JR, Porceddu PF, et al. Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms. Prog Neurobiol. 2017; 155: 149–170. https://doi.org/10.1016/j.pneurobio.2015.09.011.

Bouziane C, Filatova OG, Schrantee A, Caan MWA, Vos FM, Reneman L. White Matter by Diffusion MRI Following Methylphenidate Treatment: A Randomized Control Trial in Males with Attention-Deficit/Hyperactivity Disorder. Radiology. 2019; 293: 186–192. https://doi.org/10.1148/radiol.2019182528.

Verlaet AAJ, Breynaert A, Ceulemans B, De Bruyne T, Fransen E, Pieters L, et al. Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case–control comparison. Eur Child Adolesc Psychiatry. 2019; 28: 719–729. https://doi.org/10.1007/s00787-018-1239-4.

Alvarez-Arellano L, González-García N, Salazar-García M, Corona JC. Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder. Antioxidants. 2020; 9: 176. https://doi.org/10.3390/antiox9020176.

Beard D. The Effects Of Ritalin On Mouse And Rat Behaviors. 2020. https://conductscience.com/maze/the-effects-of-ritalin-on-mouse-and-rat-behaviors/

Shellenberg TP, Stoops WW, Lile JA, Rush CR. An update on the clinical pharmacology of methylphenidate: therapeutic efficacy, abuse potential and future considerations. Expert Rev Clin Pharmacol. 2020; 13: 825–833. https://doi.org/10.1080/17512433.2020.1796636.

Markowitz JS, Patrick KS. The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2017; 27: 678–689. https://doi.org/10.1089/cap.2017.0071.

Sabbe M, Sawchik J, Gräfe M, Wuillaume F, De Bruyn S, Van Antwerpen P, et al. Use and misuse of prescription stimulants by university students: a cross-sectional survey in the french-speaking community of Belgium, 2018. Arch Public Health. 2022; 80: 54. https://doi.org/10.1186/s13690-022-00816-3.

Kerekes N, Sanchéz-Pérez AM, Landry M. Neuroinflammation as a possible link between attention-deficit/hyperactivity disorder (ADHD) and pain. Med Hypotheses. 2021; 157: 110717. https://doi.org/10.1016/j.mehy.2021.110717.

Zimmer L. Contribution of Clinical Neuroimaging to the Understanding of the Pharmacology of Methylphenidate. Trends Pharmacol Sci. 2017; 38: 608–620. https://doi.org/10.1016/j.tips.2017.04.001.

Luethi D, Kaeser PJ, Brandt SD, Krähenbühl S, Hoener MC, Liechti ME. Pharmacological profile of methylphenidate-based designer drugs. Neuropharmacology. 2018; 134: 133–140. https://doi.org/10.1016/j.neuropharm.2017.08.020.

Moszczynska A, Callan SP. Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment. J Pharmacol Exp Ther. 2017; 362: 474–488. https://doi.org/10.1124/jpet.116.238501.

Zeng Y, Chen Y, Zhang S, Ren H, Xia J, Liu M, et al. Natural Products in Modulating Methamphetamine-Induced Neuronal Apoptosis. Front Pharmacol. 2022; 12. https://doi.org/10.3389/fphar.2021.805991.

Mozaffari S, Ramezany Yasuj S, Motaghinejad M, Motevalian M, Kheiri R. Crocin Acting as a Neuroprotective Agent against Methamphetamine-induced Neurodegeneration via CREB-BDNF Signaling Pathway. Iran J Pharm Res. 2019; 15: 745–758. https://doi.org/10.22037/ijpr.2019.2393

Ebrahimzadeh A, Moghadam SY, Rahimi H, Motaghinejad M, Motevalian M, Safari S, et al. Crocin acts as a neuroprotective mediator against methylphenidate induced neurobehavioral and neurochemical sequelae: Possible role of the CREB-BDNF signaling pathway. Acta Neurobiol Exp (Wars). 2019; 79(4): 352–366. PMID: 31885392.

Prakash V, Jaiswal N, Srivastava M. A Review on Medicinal Properties Of Centella Asiatica. Asian J Pharm Clin Res. 2017; 10: 69. https://doi.org/10.22159/ajpcr.2017.v10i10.20760.

Ali SH, Obaid QA, Awaid KG. Lemon juice antioxidant activity against oxidative stress. Baghdad Sci J. 2020; 17(1): 207–213. https://doi.org/10.21123/bsj.2020.17.1(Suppl.).0207.

Mustafa AJ, Ismail PA. Association of potent inflammatory Cytokine and Oxidative DNA Damage Biomarkers in Stomach cancer patients. Baghdad Sci J. 2022; 19(6): 1313–1325. https://doi.org/10.21123/bsj.2022.6589.

Motaghinejad M, Motevalian M, Fatima S. Mediatory role of NMDA, AMPA/kainate, GABA A and Alpha 2 receptors in topiramate neuroprotective effects against methylphenidate induced neurotoxicity in rat. Life Sci. 2017; 179: 37–53. https://doi.org/10.1016/j.lfs.2017.01.002.

Ballester J, Valentine G, Sofuoglu M. Pharmacological treatments for methamphetamine addiction: current status and future directions. Expert Rev Clin Pharmacol. 2017: 10(3): 305-314. https://doi.org/10.1080/17512433.2017.1268916.

Jiao D, liu Y, Li X, liu J, Zhao M. The role of the GABA system in amphetamine-type stimulant use disorders. Front Cell Neurosci. 2015; 9: 162. https://doi.org/10.3389/fncel.2015.00162.

Laboratory BT. Human Interleukin 6, IL-6 ELISA Kit. BT Lab; 2020. https://www.bt-laboratory.com/Upload/manual/kit/E0135Ra.pdf

Laboratory BT. Rat Tumor Necrosis Factor Α, TNF-A ELISA Kit. BT Lab. ; 2019. https://www.bt-laboratory.com/Upload/manual/kit/E0764Ra.pdf

Laboratory BT. Rat Glutathione Peroxidase 1, GPX-1 ELISA Kit. BT Lab. ;2019. https://www.bt-laboratory.com/Upload/manual/kit/E1172Ra.pdf

GraphPad Software Inc. Prism 9: Taking your analyses and graphs to higher dimensions. GraphPad Software Inc. GraphPad Software Inc.; 2020. https://www.graphpad.com/updates/prism-900-release-notes

Lee S, Lee DK. What is the proper way to apply the multiple comparison test? Korean J Anesthesiol. 2018; 71(5): 353–60. https://doi.org/10.4097/kja.d.18.00242.

Jasim NH, Mohammed YJ, Alahmed JAS, Majeed MF. Methylphenidate Hydrochloride Overdose Induces Liver Damage in Rats: The Evaluation of Histopathology and Some Antioxidant Enzymes Biomarkers. Adv Anim Vet Sci. 2023; 11: 933–938. https://doi.org/10.17582/journal.aavs/2023/11.6.933.938.

Mehrafza S, Kermanshahi S, Mostafidi S, Motaghinejad M, Motevalian M, Fatima S. Pharmacological evidence for lithium-induced neuroprotection against methamphetamine-induced neurodegeneration via Akt- 1/GSK3 and CREB-BDNF signaling pathways. Iran J Basic Med Sci. 2019; 22: 856–865. https://doi.org/10.22038/ijbms.2019.30855.7442.

Mozaffari S, Yasuj SR, Motaghinejad M, Motevalian M, Kheiri R. Crocin acting as a neuroprotective agent against methamphetamine-induced neurodegeneration via CREB-BDNF signaling pathway. Iran J Pharm Res. 2019; 18: 745–758. https://doi.org/10.22037/ijpr.2019.2393.

Taheri P, Keshavarzi S, Ebadi M, Motaghinejad M, Motevalian M. Neuroprotective Effects of Forced Exercise and Bupropion on Chronic Methamphetamine-induced Cognitive Impairment via Modulation of cAMP Response Element-binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway, Oxidative Stress, and Inflammatory Biomarkers in Rats. Adv Biomed Res. 2018; 7: 151. https://doi.org/10.4103/abr.abr_11_18.

Motaghinejad M, Motevalian M, Babalouei F, Abdollahi M, Heidari M, Madjd Z. Possible involvement of CREB/BDNF signaling pathway in neuroprotective effects of topiramate against methylphenidate induced apoptosis, oxidative stress and inflammation in isolated hippocampus of rats: Molecular, biochemical and histological evidences. Brain Res Bull. 2017; 132: 82–98. https://doi.org/10.1016/j.brainresbull.2017.05.011.

Foschiera LN, Schmitz F, Wyse ATS. Evidence of methylphenidate effect on mitochondria, redox homeostasis, and inflammatory aspects: Insights from animal studies. Prog Neuropsychopharmacol Biol Psychiatry. 2022; 116: 110518. https://doi.org/10.1016/j.pnpbp.2022.110518.

Wang J, Lu C, Zheng L, Zhang J. Peripheral Inflammatory Biomarkers of Methamphetamine Withdrawal Patients Based on the Neuro-Inflammation Hypothesis: The Possible Improvement Effect of Exercise. Front Psychiatry. 2021; 12. https://doi.org/10.3389/fpsyt.2021.795073.

Corona JC. Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder. Antioxidants. 2020; 9: 1039. https://doi.org/10.3390/antiox9111039.

Ding J, Huang J, Tang X, Shen L, Hu S, He J, et al. Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus. Front Cell Neurosci. 2022; 16. https://doi.org/10.3389/fncel.2022.1003617.

Levin SG, Godukhin O V. Modulating effect of cytokines on mechanisms of synaptic plasticity in the brain. Biochemistry (Moscow). 2017; 82: 264–274. https://doi.org/10.1134/S000629791703004X.

Namba MD, Leyrer-Jackson JM, Nagy EK, Olive MF, Neisewander JL. Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities. Front Neurosci. 2021; 15. https://doi.org/10.3389/fnins.2021.650785.

Hao L, Yang Z, Lei J. Underlying mechanisms of cooperativity, input specificity, and associativity of long-term potentiation through a positive feedback of local protein synthesis. Front Comput Neurosci. 2018; 12. https://doi.org/10.3389/fncom.2018.00025.

Sumi T, Harada K. Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors. Sci Rep. 2020; 10. https://doi.org/10.1038/s41598-020-71528-3.

Lyra e Silva NM, Gonçalves RA, Pascoal TA, Lima-Filho RAS, Resende E de PF, Vieira ELM, et al. Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Transl Psychiatry. 2021; 11. https://doi.org/10.1038/s41398-021-01349-z.

Downloads

Issue

Section

article

How to Cite

1.
The Effect of Chronic Administration of Amphetamine-Type Stimulants on Oxidative Stress and Inflammation in Wistar Rats. Baghdad Sci.J [Internet]. [cited 2024 Apr. 30];21(7). Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/9170