The protective effects of sumatriptan on vincristine - induced peripheral neuropathy in a rat model

Authors

Mina Khalilzadeh, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mkhalilzadeh@razi.tums.ac.ir.
Ghodratollah Panahi, Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Amir Rashidian, Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Reza Hadian, School of Rehabilitation, Brain and Spinal Injury Research Center (BASIR), Tehran University of Medical Sciences, International Campus (TUMS, TUMS-IC), Tehran, Iran.
Alireza Abdollahi, Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Khashayar Afshari, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Saeed Shakiba, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Abbas Norouzi-Javidan, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Nastaran Rahimi, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Majid Momeny, Cancer Cell Signaling, Turku Center for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
Ahmad Reza Dehpour, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.

Document Type

Article

Publication Title

Neurotoxicology

Abstract

Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been limited due to its peripheral neuropathy toxicity. Sumatriptan, which is an anti-migraine agent is a specific agonist for 5-hydroxytryptamine 1B, 1D (5HT1B, 1D) receptors. Several studies have shown that sumatriptan exerts anti-inflammatory and immunomodulatory properties. This study aimed to investigate the effects of sumatriptan on VCR-induced peripheral neuropathy in a rat model. Male Wistar rats were intraperitoneally injected with VCR and normal saline four times per week for 2 weeks. In the treatment group, sumatriptan (1 mg/kg) was administered intraperitoneally 30 min prior to VCR injection every day. Mortality rate, weight variations and histopathological changes were monitored. Hot plate, tail flick and motor nerve conduction velocity (MNCV) tests were used to evaluate sensory and motor neuropathy. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and caspase-3 in the dorsal ganglion root were assessed by quantitative reverse transcription-PCR (qRT-PCR). Moreover, the protein levels of p65 nuclear factor kappa B (NF- B) and phospho-p65 NF- B were examined by Western blot analysis. Co-administration of sumatriptan with VCR significantly reversed alterations in the hot plate, tail flick threshold and sciatic MNCV induced by VCR and also prevented mixed sensory-motor neuropathy, as indicated by better general conditions, behavioral and electrophysiological results. In addition, sumatriptan improved the body weight loss caused by VCR. The mRNA levels of TNF-α, IL-1β and caspase-3 were significantly diminished in the treatment group. These findings were confirmed by histopathological analysis. In conclusion, this study demonstrated that sumatriptan significantly attenuated VCR-induced neuropathy and could be considered as a neuroprotective agent to prevent the VCR-induced neuropathy.

First Page

279

Last Page

286

DOI

10.1016/j.neuro.2018.06.012

Publication Date

7-1-2018

Recommended Citation

Khalilzadeh, Mina; Panahi, Ghodratollah; Rashidian, Amir; Hadian, Mohammad Reza; Abdollahi, Alireza; Afshari, Khashayar; Shakiba, Saeed; Norouzi-Javidan, Abbas; Rahimi, Nastaran; Momeny, Majid; and Dehpour, Ahmad Reza, "The protective effects of sumatriptan on vincristine - induced peripheral neuropathy in a rat model" (2018). Internal Medicine. 321.
https://scholar.bridgeporthospital.org/internal_medicine/321

Identifier

29958920 (pubmed); 10.1016/j.neuro.2018.06.012 (doi); S0161-813X(18)30236-5 (pii)