Effects of edaravone on hypoxia-induced lethality in male Swiss albino mice

Authors

  • Fatemeh Shaki Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran
  • Mina Mokhtaran Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran
  • Maedeh Raei Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  • Alireza Razavi Research Center for Clinical Virology, Tehran University of Medical Science, Tehran, Iran
  • Amir Shamshirian Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  • Shahram Eslami Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran
  • Danial Shamshirian Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Mohammad Ali Ebrahimzadeh Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Science, Sari, Iran

DOI:

https://doi.org/10.13181/mji.oa.257997

Keywords:

antihypoxia, asphyxia hypoxia, oxidative stress

Abstract

BACKGROUND Edaravone has recently been used to treat acute cerebral infarction. This study aimed to evaluate the protective effects of edaravone against hypoxia-induced lethality and oxidative stress in mice using 3 experimental models of hypoxia: asphyxia, circulatory, and hemic hypoxia.

METHODS 60 Swiss albino mice from the animal facility of Mazandaran University of Medical Sciences, Iran, were randomly housed in groups of 10 during January–March 2020 and received edaravone for 4 consecutive days. After inducing hypoxia, oxidative stress, lipid peroxidation (LPO), and glutathione (GSH) content were assessed.

RESULTS The findings showed significant protective effects of edaravone in all hypoxia models, with the strongest effects in asphyxia and circulatory hypoxia, showing a dose-dependent response. It prolonged survival time at 2.5 mg/kg by 26.08 (0.79) min (p = 0.031) In addition, edaravone significantly inhibited hypoxia-induced oxidative stress (LPO and GSH oxidation) in all 3 hypoxia models.

CONCLUSIONS Edaravone exhibits an excellent protective effect against different models of hypoxia by decreasing oxidative stress in brain tissue. In addition, the results showed dose-dependent effects of edaravone in the asphyxia and circulatory hypoxia models. Antioxidant activity might be a proposed mechanism for the anti-hypoxic activity of this drug.

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References

Della Rocca Y, Fonticoli L, Rajan TS, Trubiani O, Caputi S, Diomede F, et al. Hypoxia: molecular pathophysiological mechanisms in human diseases. J Physiol Biochem. 2022;78(4):739-52. https://doi.org/10.1007/s13105-022-00912-6

Polkam N, Ramaswamy VR, Rayam P, Allaka TR, Anantaraju HS, Dharmarajan S, et al. Synthesis, molecular properties prediction and anticancer, antioxidant evaluation of new edaravone derivatives. Bioorg Med Chem Lett. 2016;26(10):2562-8. https://doi.org/10.1016/j.bmcl.2016.03.024

Rohlik DL, Patel E, Gilbert NC, Offenbacher AR, Garcia BL. Investigating membrane-binding properties of lipoxygenases using surface plasmon resonance. Biochem Biophys Res Commun. 2023;670:47-54. https://doi.org/10.1016/j.bbrc.2023.05.066

Amado B, Melo L, Pinto R, Lobo A, Barros P, Gomes JR. Ischemic stroke, lessons from the past towards effective preclinical models. Biomedicines. 2022;10(10):2561. https://doi.org/10.3390/biomedicines10102561

Li SY, Fu ZJ, Lo AC. Hypoxia-induced oxidative stress in ischemic retinopathy. Oxid Med Cell Longev. 2012;2012:426769. https://doi.org/10.1155/2012/426769

Kikuchi K, Tancharoen S, Takeshige N, Yoshitomi M, Morioka M, Murai Y, et al. The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease. Int J Mol Sci. 2013;14(7):13909-30. https://doi.org/10.3390/ijms140713909

Huang M, Mo Y, Lei H, Chen M. Edaravone: a possible treatment for acute lung injury. Int J Gen Med. 2024;17:3975-86. https://doi.org/10.2147/IJGM.S467891

Uchiyama M, Tojo K, Yazawa T, Ota S, Goto T, Kurahashi K. Edaravone prevents lung injury induced by hepatic ischemia-reperfusion. J Surg Res. 2015;194(2):551-7. https://doi.org/10.1016/j.jss.2014.11.011

Kawamoto T, Sasai K. Edaravone exerts protective effects on mice intestinal injury without interfering with the anti-tumor effects of radiation. Curr Issues Mol Biol. 2023;45(7):5362-72. https://doi.org/10.3390/cimb45070340

Mohammadi H, Shamshirian A, Eslami S, Shamshirian D, Ebrahimzadeh MA. Magnesium sulfate attenuates lethality and oxidative damage induced by different models of hypoxia in mice. Biomed Res Int. 2020;2020:2624734. https://doi.org/10.1155/2020/2624734

Sucha M, Benediktova S, Tichanek F, Jedlicka J, Kapl S, Jelinkova D, et al. Experimental treatment with edaravone in a mouse model of spinocerebellar ataxia 1. Int J Mol Sci. 2023;24(13):10689. https://doi.org/10.3390/ijms241310689

Dong S, Lyu X, Yuan S, Wang S, Li W, Chen Z, et al. Oxidative stress: a critical hint in ionizing radiation induced pyroptosis. Rad Med Prot. 2020;1(4):179-85. https://doi.org/10.1016/j.radmp.2020.10.001

Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014;94(2):329-54. https://doi.org/10.1152/physrev.00040.2012

Silva D, Rocha R, Correia AS, Mota B, Madeira MD, Vale N, et al. Repurposed edaravone, metformin, and perampanel as a potential treatment for hypoxia-ischemia encephalopathy: an in vitro study. Biomedicines. 2022;10(12):3043. https://doi.org/10.3390/biomedicines10123043

Zhao M, Zhu P, Fujino M, Zhuang J, Guo H, Sheikh I, et al. Oxidative stress in hypoxic-ischemic encephalopathy: molecular mechanisms and therapeutic strategies. Int J Mol Sci. 2016;17(12):2078. https://doi.org/10.3390/ijms17122078

Sun YY, Li Y, Wali B, Li Y, Lee J, Heinmiller A, et al. Prophylactic edaravone prevents transient hypoxic-ischemic brain injury: implications for perioperative neuroprotection. Stroke. 2015;46(7):1947-55. https://doi.org/10.1161/STROKEAHA.115.009162

Ashok A, Andrabi SS, Mansoor S, Kuang Y, Kwon BK, Labhasetwar V. Antioxidant therapy in oxidative stress-induced neurodegenerative diseases: role of nanoparticle-based drug delivery systems in clinical translation. Antioxidants (Basel). 2022;11(2):408. https://doi.org/10.3390/antiox11020408

Rumman M, Pandey S, Singh B, Gupta M, Mahdi AA. Genistein suppresses microglial activation and inhibits apoptosis in different brain regions of hypoxia-exposed mice model of amnesia. Metab Brain Dis. 2022;37(7):2521-32. https://doi.org/10.1007/s11011-022-01039-9

Zeng Z, Hill-Yardin EL, Williams D, O'Brien T, Serelis A, French CR. Effect of phenytoin on sodium conductances in rat hippocampal CA1 pyramidal neurons. J Neurophysiol. 2016;116(4):1924-36. https://doi.org/10.1152/jn.01060.2015

Puljko B, Stojanović M, Ilic K, Kalanj-Bognar S, Mlinac-Jerkovic K. Start me up: how can surrounding gangliosides affect sodium-potassium ATPase activity and steer towards pathological ion imbalance in neurons? Biomedicines. 2022;10(7):1518. https://doi.org/10.3390/biomedicines10071518

Joyce W, Williams CJ, Iversen S, Henriksen PG, Bayley M, Wang T. The effects of endogenous and exogenous catecholamines on hypoxic cardiac performance in red-bellied piranhas. J Exp Zool A Ecol Integr Physiol. 2019;331(1):27-37. https://doi.org/10.1002/jez.2233

Bețiu AM, Noveanu L, Hâncu IM, Lascu A, Petrescu L, Maack C, et al. Mitochondrial effects of common cardiovascular medications: the good, the bad and the mixed. Int J Mol Sci. 2022;23(21):13653. https://doi.org/10.3390/ijms232113653

Baitharu I, Jain V, Deep SN, Shroff S, Sahu JK, Naik PK, et al. Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia. PloS one. 2014;9(10):e105311. https://doi.org/10.1371/journal.pone.0105311

Mitroshina EV, Savyuk MO, Ponimaskin E, Vedunova MV. Hypoxia-inducible factor (HIF) in ischemic stroke and neurodegenerative disease. Front Cell Dev Biol. 2021;9:703084. https://doi.org/10.3389/fcell.2021.703084

Dickmeiß J, Henning Y, Stahlke S, Weber T, Theiss C, Matschke V. Differential protective effects of edaravone in cerebellar and hippocampal ischemic injury models. Cerebellum. 2025;24(2):49. https://doi.org/10.1007/s12311-025-01804-3

Published

2025-09-30

How to Cite

1.
Shaki F, Mokhtaran M, Raei M, Razavi A, Shamshirian A, Eslami S, et al. Effects of edaravone on hypoxia-induced lethality in male Swiss albino mice. Med J Indones [Internet]. 2025 Sep. 30 [cited 2025 Oct. 9];34(3):146-50. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/7997

Issue

Section

Basic Medical Research