The neuroprotective effect of tropisetron on vincristine-induced neurotoxicity |
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| Institution: | 1. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran;2. Department of Pharmacology and Toxicology, University of Otago, P.O. Box 913, Dunedin, New Zealand;3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Pharmacology, Islamic Azad University of Pharmaceutical Sciences, Tehran, Iran;5. Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Germany;6. Department of Pathology, Tehran University of Medical Science, Tehran, Iran;7. Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Human Anatomy, Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlandia, MG, Brazil;2. Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia (UFU), Uberlandia, MG, Brazil;3. Department of Physiology, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil;1. Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brazil;2. Department of Otorhinolaryngology, Hospital Central da Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil;3. Department of Immunology, Universidade de São Paulo (USP), São Paulo, SP, Brazil;4. Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP, Brazil;5. Department of Gastroenterology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil;6. School of Medicine, Universidade de São Paulo (USP), São Paulo, SP, Brazil;1. Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand;2. College of Medicine and Medical Sciences, Department of Molecular Medicine, Nanomedicine Unit, Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders, Arabian Gulf University, Manama, Bahrain |
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| Abstract: | Vincristine (VCR) peripheral neuropathy is a dose-limiting side effect. Several studies have shown that tropisetron, a 5-HT3 receptor antagonist, exerts anti-inflammatory and immunomodulatory properties. Current study was designed to investigate a suppressive effect of tropisetron on VCR-induced neuropathy and whether this effect exerts through the 5-HT3 receptor or not.Neuropathy was induced in rats by administration of vincristine (0.5 mg/kg, 3 intraperitoneal injections on alternate days) and in treatment group, tropisetron (3 mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT3 receptor agonist (15 mg/kg); tropisetron (3 mg/kg) plus mCPBG (15 mg/kg); granisetron, another selective 5-HT3 receptor antagonist (3 mg/kg) were administered intraperitoneally 1 h prior to vincristine injection. Hot plate, open field tests (total distance moved, mean velocity and percentage of total duration of the movement) and motor nerve conduction velocity (MNCV) were performed to evaluate the sensory and motor neuropathy. Further, plasma levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) and the level of TNF-α in sciatic nerve were assessed as well as histological examination.In only VCR-treated rats hot plate latencies were significantly increased, total distance moved, mean velocity, total duration of the movement and sciatic MNCV significantly decreased compared with control. In tropisetron and tropisetron plus mCPBG groups, one injection of tropisetron prior to each VCR injection robustly diminished TNF-α and IL-2 levels, and also prevented mixed sensory-motor neuropathy, as indicated by less mortality rate, better general conditions, behavioral and electrophysiological studies. Moreover, pathological evidence confirmed the results obtained from other findings. But granisetron and mCPBG had no significant effect on the mentioned parameters.In conclusion, these studies demonstrate that tropisetron significantly suppressed VCR-induced neuropathy and could be a neuroprotective agent for prevention of VCR-induced neuropathy via a receptor-independent pathway. |
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| Keywords: | Vincristine Tropisetron Granisetron Peripheral neuropathy Neuroprotective |
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