Shahid Beheshti University of Medical Sciences, Iran
  • Register
  • Login

International Journal of Medical Toxicology and Forensic Medicine

  • Home
  • About
    • About the Journal
    • Aims and Scope
    • Editorial Team
    • Contact
  • Issues
    • Current
    • Archives
  • Indexing & Abstracting
  • Editorial Policies
    • Peer Review Process
    • Ethical Codes: Medical Research
    • Principles of Publishing Ethics
    • Conflicts of Interest
    • Publication Frequency
    • Open Access Policy
    • CrossMark Policy
    • Article Processing Charges
    • Privacy Statement
  • Announcements
  • Register
  • Login
  • Author Guidelines
Advanced Search
  1. Home
  2. Archives
  3. Vol. 14 No. 03 (2024)
  4. Original Article

Vol. 14 No. 03 (2024)

August 2024

Muscular Injection of Botox Exacerbates Seizures Through TNF-alpha and Oxidative Stress in Mice

  • Majid Hassanpourezatti
  • Mehdi Hosseini

International Journal of Medical Toxicology and Forensic Medicine, Vol. 14 No. 03 (2024), 6 August 2024
https://doi.org/10.32598/ijmtfm.v14i03.43944 Published: 08/06/2024

  • View Article
  • Download
  • Cite
  • References
  • Statastics
  • Share

Abstract

Background: Recent research has revealed the central adverse effects of Botox after intramuscular injection. The aim of this study was to examine the role of brain oxidative stress factors and circulatory cytokines as indicators of the severity of seizures following acute intramuscular (IM) injection of Botox in mice.
Methods: Botox (1, 5 and 30 U, IM) was injected 60 minutes before inducing maximal electroshock (MES) seizures. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels were measured in the brain. Tumor necrosis factor-alpha (TNF-α) levels were also determined in the serum. The motor coordination was assessed after Botox administration by using the chimney test.
Results: Botox (5 and 10 U/kg, IM) significantly reduced the duration of hindlimb extension (HLE) and elevated levels of NO and MDA in the brain compared to the seizure group. Additionally, the administration of Botox (1 and 5 U, IM) increased the level of GSH in the brain, while 30 U decreased it. All Botox dosages demonstrated an enhancing effect on serum TNF-α levels compared to the seizure group. Botox at 5 and 30 U induced locomotor incoordination in mice.
Conclusion: Our results showed that IM injection of Botox can lead to the exacerbation of tonic-clonic seizures by stimulating oxidative stress in the brain and increasing circulating TNF-α levels in mice.

Keywords:
  • Botulinum toxins
  • Seizures
  • Oxidative stress
  • Neuroinflammation
  • Brain
  • pdf

How to Cite

Hassanpourezatti, M., & Hosseini, M. (2024). Muscular Injection of Botox Exacerbates Seizures Through TNF-alpha and Oxidative Stress in Mice. International Journal of Medical Toxicology and Forensic Medicine, 14(03). https://doi.org/10.32598/ijmtfm.v14i03.43944
  • ACM
  • ACS
  • APA
  • ABNT
  • Chicago
  • Harvard
  • IEEE
  • MLA
  • Turabian
  • Vancouver
  • Endnote/Zotero/Mendeley (RIS)
  • BibTeX

References

Madireddy S, Madireddy S. Therapeutic strategies to ameliorate neuronal damage in epilepsy by regulating oxidative stress, mitochondrial dysfunction, and neuroinflammation. Brain Sciences. 2023; 13(5):784. [DOI:10.3390/brainsci13050784] [PMID]

Kobylarek D, Iwanowski P, Lewandowska Z, Limphaibool N, Szafranek S, Labrzycka A, et al. Advances in the potential biomarkers of epilepsy. Frontiers in Neurology. 2019; 10:685. [DOI:10.3389/fneur.2019.00685] [PMID]

Fabisiak T, Patel M. Crosstalk between neuroinflammation and oxidative stress in epilepsy. Frontiers in Cell and Developmental Biology. 2022; 10:976953. [DOI:10.3389/fcell.2022.976953] [PMID]

Ilhan A, Aladag MA, Kocer A, Boluk A, Gurel A, Armutcu F. Erdosteine ameliorates PTZ-induced oxidative stress in mice seizure model. Brain Research Bulletin. 2005; 65(6):495-9. [DOI:10.1016/j.brainresbull.2005.02.027] [PMID]

Riazi K, Galic MA, Kuzmiski JB, Ho W, Sharkey KA, Pittman QJ. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(44):17151-6. [DOI:10.1073/pnas.0806682105] [PMID]

Banote RK, Akel S, Zelano J. Blood biomarkers in epilepsy. Acta Neurologica Scandinavica. 2022; 146(4):362-8. [DOI:10.1111/ane.13616] [PMID]

Borowicz-Reutt KK, Czuczwar SJ. Role of oxidative stress in epileptogenesis and potential implications for therapy.Pharmacological Reports. 2020; 72(5):1218-26. [DOI:10.1007/s43440-020-00143-w] [PMID]

Pottoo FH, Salahuddin M, Khan FA, Al Dhamen MA, Alsaeed WJ, Gomaa MS, et al. Combinatorial regimen of carbamazepine and imipramine exhibits synergism against grandmal epilepsy in rats: Inhibition of pro-inflammatory cytokines and PI3K/Akt/mTOR signaling pathway. Pharmaceuticals (Basel). 2021; 14(11):1204. [DOI:10.3390/ph14111204] [PMID]

Palazón-García R, Benavente-Valdepeñas AM. Botulinum Toxin: From poison to possible treatment for spasticity in spinal cord injury. International Journal of Molecular Sciences. 2021; 22(9):4886. [DOI:10.3390/ijms22094886] [PMID]

Sim WS. Application of botulinum toxin in pain management. The Korean Journal of Pain. 2011; 24(1):1-6. [DOI:10.3344/kjp.2011.24.1.1] [PMID]

Bröer S, Zolkowska D, Gernert M, Rogawski MA. Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat. Neuroscience. 2013; 252:253-61. [DOI:10.1016/j.neuroscience.2013.07.050] [PMID]

Tsui JK. Botulinum toxin as a therapeutic agent. Pharmacology & Therapeutics. 1996; 72(1):13-24. [DOI:10.1016/S0163-7258(96)00091-5] [PMID]

Jensen DB, Klingenberg S, Dimintiyanova KP, Wienecke J, Meehan CF. Intramuscular Botulinum toxin A injections induce central changes to axon initial segments and cholinergic boutons on spinal motoneurones in rats. Scientific Reports. 2020; 10(1):893. [DOI:10.1038/s41598-020-57699-z] [PMID]

Weise D, Weise CM, Naumann M. Central effects of botulinum neurotoxin-evidence from human studies. Toxins (Basel). 2019; 11(1):21. [DOI:10.3390/toxins11010021] [PMID]

Vinehout K, Tynes K, Sotelo MR, Hyngstrom AS, McGuire JR, Schmit BD. Changes in cortical activity in stroke survivors undergoing botulinum neurotoxin therapy for treatment of focal spasticity. Frontiers in Rehabilitation Sciences. 2021; 2:735819. [PMID]

Moskiewicz D, Mraz M, Chamela-Bilińska D. Botulinum toxin and dynamic splint restore grasping function after stroke: A case report. International Journal of Environmental Research and Public Health. 2023; 20(6):4873. [DOI:10.3390/ijerph20064873] [PMID]

Delnooz CC, Pasman JW, Beckmann CF, van de Warrenburg BP. Task-free functional MRI in cervical dystonia reveals multi-network changes that partially normalize with Botulinum toxin. Plos One. 2013; 8(5):e62877. [DOI:10.1371/journal.pone.0062877] [PMID]

Delnooz CC, Pasman JW, Beckmann CF, van de Warrenburg BP. Altered striatal and pallidal connectivity in cervical dystonia. Brain Structure & Function. 2015; 220(1):513-23. [DOI:10.1007/s00429-013-0671-y] [PMID]

Pingel J, Pacolet A, Elfving B, Ledri LN. Intramuscular Botox/A injections cause an inflammatory response in the muscle tissue of rats. European Journal of Inflammation. 2021; 19:1-10. [DOI:10.1177/20587392211039942]

Luvisetto S. Botulinum neurotoxins in central nervous system: An overview from animal models to human therapy. Toxins (Basel). 2021; 13(11):751. [DOI:10.3390/toxins13110751] [PMID]

Kim YJ, Kim JH, Lee KJ, Choi MM, Kim YH, Rhie GE, et al. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. Plos One. 2015; 10(4):e0120840. [DOI:10.1371/journal.pone.0120840] [PMID]

Kato K, Akaike N, Kohda T, Torii Y, Goto Y, Harakawa T, et al. Botulinum neurotoxin A2 reduces incidence of seizures in mouse models of temporal lobe epilepsy. Toxicon. 2013; 74:109-15. [DOI:10.1016/j.toxicon.2013.07.027] [PMID]

Costantin L, Bozzi Y, Richichi C, Viegi A, Antonucci F, Funicello M, et al. Antiepileptic effects of botulinum neurotoxin E. The Journal of Neuroscience. 2005; 25(8):1943-51. [DOI:10.1523/JNEUROSCI.4402-04.2005] [PMID]

Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel). 2017; 9(9):260. [DOI:10.3390/toxins9090260] [PMID]

Hong B, Yao LL, Hu XY. None detectable retrograde transport of Chinese botulinum toxin type A in mice by single intramuscular injection. International Journal of Clinical and Experimental Medicine. 2015; 8(9):15815-21. [PMID]

Yesudhas A, Roshan SA, Radhakrishnan RK, Abirami GPP, Manickam N, Selvaraj K, et al. Intramuscular injection of Botox® boosts learning and memory in adult mice in association with enriched circulation of platelets and enhanced density of pyramidal neurons in the hippocampus. Neurochemical Research. 2020; 45(12):2856-67. [DOI:10.1007/s11064-020-03133-9] [PMID]

Matak I, Riederer P, Lacković Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochemistry International. 2012; 61(2):236-9. [DOI:10.1016/j.neuint.2012.05.001] [PMID]

Zarnowska I, Luszczki JJ, Zarnowski T, Wlaz P, Czuczwar SJ, Gasior M. Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice. Metabolic Brain Disease. 2017; 32(2):351-8. [DOI:10.1007/s11011-016-9900-4] [PMID]

Samarghandian S, Rajabi S, Aschner M, Noferesti V, Farkhondeh T. Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation. Toxicology Reports. 2022; 9:2050-4. [DOI:10.1016/j.toxrep.2022.11.005] [PMID]

Ramazani N, Mahd Gharebagh F, Soleimanzadeh A, Arslan HO, Keles E, Gradinarska-Yanakieva DG, et al. The influence of L-proline and fulvic acid on oxidative stress and semen quality of buffalo bull semen following cryopreservation. Veterinary Medicine and Science. 2023; 9(4):1791-802. [DOI:10.1002/vms3.1158] [PMID]

Luszczki JJ, Wojda E, Andres-Mach M, Cisowski W, Glensk M, Glowniak K, et al. Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: A comparative study. Epilepsy Research. 2009; 85(2-3):293-9. [DOI:10.1016/j.eplepsyres.2009.03.027] [PMID]

Lee WI, Carney PW, Hughes AJ, Archer JS. Refractory focal motor seizures controlled with intramuscular botulinum toxin. Epilepsy Research. 2017; 133:93-7. [DOI:10.1016/j.eplepsyres.2017.04.009] [PMID]

Montastruc J, Marque P, Moulis F, Bourg V, Lambert V, Durrieu G, et al. Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: A pharmaco-epidemiological study in VigiBase. Developmental Medicine and Child Neurology. 2017; 59(3):329-34. [DOI:10.1111/dmcn.13286] [PMID]

Caleo M, Restani L. Exploiting botulinum neurotoxins for the study of brain physiology and pathology. Toxins (Basel). 2018; 10(5):175. [DOI:10.3390/toxins10050175] [PMID]

Pieróg M, Socała K, Wyska E, Poleszak E, Wlaź P. Effect of ellagic acid on seizure threshold in two acute seizure tests in mice. Molecules. 2021; 26(16):4841. [DOI:10.3390/molecules26164841] [PMID]

Reiter RJ, Manchester LC, Tan DX. Neurotoxins: Free radical mechanisms and melatonin protection. Current Neuropharmacology. 2010; 8(3):194-210. [DOI:10.2174/157015910792246236] [PMID]

Maupu C, Enderlin J, Igert A, Oger M, Auvin S, Hassan-Abdi R, et al. Diisopropylfluorophosphate-induced status epilepticus drives complex glial cell phenotypes in adult male mice. Neurobiology of Disease. 2021; 152:105276. [DOI:10.1016/j.nbd.2021.105276] [PMID]

Gioltzoglou T, Cordivari C, Lee PJ, Hanna MG, Lees AJ. Problems with botulinum toxin treatment in mitochondrial cytopathy: Case report and review of the literature. Journal of Neurology, Neurosurgery, and Psychiatry. 2005; 76(11):1594-6. [DOI:10.1136/jnnp.2004.057661] [PMID]

Lorigados Pedre L, Gallardo JM, Morales Chacón LM, Vega García A, Flores-Mendoza M, Neri-Gómez T, et al. Oxidative stress in patients with drug resistant partial complex seizure. Behavioral Sciences (Basel). 2018; 8(6):59. [DOI:10.3390/bs8060059] [PMID]

Arai Y, Maeda S, Higuchi H, Tomoyasu Y, Shimada M, Miyawaki T. Effects of midazolam and phenobarbital on brain oxidative reactions induced by pentylenetetrazole in a convulsion model. Immunopharmacology and Immunotoxicology,. 2012; 34(2):216-21. [DOI:10.3109/08923973.2011.595417] [PMID]

Ho YH, Lin YT, Wu CW, Chao YM, Chang AY, Chan JY. Peripheral inflammation increases seizure susceptibility via the induction of neuroinflammation and oxidative stress in the hippocampus. Journal of Biomedical Science. 2015; 22(1):46. [DOI:10.1186/s12929-015-0157-8] [PMID]

Chen Y, Nagib MM, Yasmen N, Sluter MN, Littlejohn TL, Yu Y, et al. Neuroinflammatory mediators in acquired epilepsy: An update. Inflammation Research. 2023; 72(4):683-701. [DOI:10.1007/s00011-023-01700-8] [PMID]

Olowe R, Sandouka S, Saadi A, Shekh-Ahmad T. Approaches for reactive oxygen species and oxidative stress quantification in epilepsy. Antioxidants (Basel). 2020; 9(10):990. [DOI:10.3390/antiox9100990] [PMID]

Hazany S, DeClouette B, Lowe J, Hwang DH, Kim PE, Bluml S, et al. Brain glutathione increase and seizure burden decrease in patients with intractable epilepsy on ketogenic diet. Journal of Epilepsy Research. 2023; 13(2):63–4. [DOI:10.14581/jer.23001.e1] [PMID]

Yesudhas A, Radhakrishnan RK, Sukesh A, Ravichandran S, Manickam N, Kandasamy M. Botox® counteracts the innate anxiety-related behaviours in correlation with increased activities of key antioxidant enzymes in the hippocampus of ageing experimental mice. Biochemical and Biophysical Research Communications. 2021; 569:54-60. [DOI:10.1016/j.bbrc.2021.06.071] [PMID]

Hazany S, DeClouette B, Lowe J, Hwang DH, Kim PE, Bluml S, et al. Brain glutathione increase and seizure burden decrease in patients with intractable epilepsy on ketogenic diet. Journal of Epilepsy Research. 2023; 13(1):1-6. [DOI:10.14581/jer.23001] [PMID]

Nageib M, Zahran MH, El-Hefnawy AS, Barakat N, Awadalla A, Aamer HG, et al. Low energy shock wave-delivered intravesical Botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder. Neurourology and Urodynamics. 2020; 39(8):2447-54. [DOI:10.1002/nau.24511] [PMID]

Maniu I, Costea R, Maniu G, Neamtu BM. Inflammatory Biomarkers in Febrile Seizure: A comprehensive bibliometric, review and visualization analysis. Brain Sciences. 2021; 11(8):1077. [DOI:10.3390/brainsci11081077] [PMID]

Ali DM, Abdelzaher WY, Abdel-Hafez S. Evaluation of the rivastigmine role against botulinum toxin-A-induced osteoporosis in albino rats: A biochemical, histological, and immunohistochemical study. Human & Experimental Toxicology. 2018; 37(12):1323-35. [DOI:10.1177/0960327118774941] [PMID]

  • Abstract Viewed: 1483 times
  • pdf Downloaded: 408 times

Download Statastics

  • Linkedin
  • Twitter
  • Facebook
  • Google Plus
  • Telegram

Developed By

Open Journal Systems

Information

  • For Readers
  • For Authors
  • For Librarians

Browse

Make a Submission

Make a Submission
  • Home
  • Archives
  • Submissions
  • About the Journal
  • Editorial Team
  • Contact

 

Copyright  The Author(s); This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-By-NC), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

       

Powered by OJSPlus