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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1467788
This article is part of the Research Topic Plant and Fungal Extracts and Metabolites in Neurotherapy: Exploring Their Pharmacology and Potential Clinical Uses View all 7 articles

Anti-Neuropathic Effects Of Astaxanthin In A Rat Model Of Chronic Constriction Injury: Passing Through Opioid/Benzodiazepine Receptors And Relevance To Its Antioxidant And Anti-Inflammatory Effects

Provisionally accepted
Boshra Hashemi Boshra Hashemi 1Sajad Fakhri Sajad Fakhri 2*Amir Kiani Amir Kiani 2,3Fatemeh Abbaszadeh Fatemeh Abbaszadeh 4Shahram Miraghaee Shahram Miraghaee 5Mohammad Mohammadi Mohammad Mohammadi 6Javier Echeverria Javier Echeverria 7*
  • 1 Student Research Committee, Kermanshah university of Medical Sciences, Kermansha, Iran
  • 2 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Kerman, Iran
  • 3 Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Kerman, Iran
  • 4 Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Alborz, Iran
  • 5 Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Kerman, Iran
  • 6 Department of Radiology and Nuclear Medicine, School of Paramedical Sciences, Kermanshah University of Medical Sciences,, Kermanshah, Iran
  • 7 University of Santiago, Santiago, Chile

The final, formatted version of the article will be published soon.

    Neuropathic pain is a debilitating neurological disorder and is on the rise. Since no effective treatment has been so far approved to combat the complex pathological mechanisms behind neuropathic pain, finding new therapeutic candidates is of great importance. Astaxanthin (AST) is a carotenoid with strong antioxidant, and anti-inflammatory activities. The present research aimed to evaluate the ameliorative effects of AST on a rat model of neuropathic pain.To induce neuropathic pain, a chronic constriction injury (CCI) model was employed.Accordingly, Wistar rats were divided into nine groups of six including sham, negative control group (CCI), positive control group gabapentin (100 mg/kg), AST (5, 10 mg/kg), flumazenil (0.5 mg/kg), naloxone (0.1 mg/kg), AST (10 mg/kg) + flumazenil (0.5 mg/kg), and AST (10 mg/kg) + naloxone (0.1 mg/kg) were administered intraperitoneally on days 1, 3, 5, 7, 10, and 14. To check the experimental signs of neuropathic pain and motor dysfunction, hot plate, acetone drop, and open field tests were used at the same time points. Additionally, biochemical assay and zymography were done on days 7 and 14 to assess the changes in catalase, glutathione and nitrite, as well as matrix metalloproteinases (MMP-2 and MMP-9). Besides, histological evaluations were performed for tissue damages on days 7 and 14.Results indicated that intraperitoneal injection of AST improved allodynia, hyperalgesia, and locomotor activity after CCI. AST also increased catalase and glutathione while suppressing nitrite, MMP-2, and MMP-9 activity through opioid/benzodiazepine receptors.The results highlighted AST as a promising candidate against neuropathic pain with beneficial effects on motor function by suppressing inflammatory mediators, and augmenting antioxidant factors, passing through opioid/benzodiazepine receptors.

    Keywords: Astaxanthin, Chronic constriction injury, inflammation, oxidative stress, Opioid receptor, Benzodiazepine receptor, neuropathic pain AST, astaxanthin, AUC, area under the curve, CCI, chronic constriction injury, DMSO, dimethylsulfoxide, DTNB, 5,5'-dithio-bis(2-nitrobenzoic acid), FLU, flumazenil, H2O2, hydrogen peroxide, MMP, matrix metalloproteinase

    Received: 20 Jul 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Hashemi, Fakhri, Kiani, Abbaszadeh, Miraghaee, Mohammadi and Echeverria. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Sajad Fakhri, Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Kerman, Iran
    Javier Echeverria, University of Santiago, Santiago, Chile

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