The Protective Effect of Modafinil on Vincristine-induced Peripheral Neuropathy in Rats: A Possible Role for TRPA1 receptors
- سال انتشار: 1398
- محل انتشار: پانزدهمین همایش سراسری سم شناسی ایران
- کد COI اختصاصی: TOXICOLOGY15_252
- زبان مقاله: انگلیسی
- تعداد مشاهده: 562
نویسندگان
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran- Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranBrain and Spinal Cord Injury Research Center, Neur
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranBrain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Department of Pathology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
Department of Toxicology-Pharmacology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, IranBrain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
چکیده
Aim: Vincristine (VCR) as an anticancer agent for leukemia and lymphoma, can lead to painful peripheral neuropathy. This study was carried out to assess the efficacy of modafinil, a central nervous system stimulant, on VCR-induced neuropathy in rats.Methods: Neuropathy was induced by intraperitoneal injections of VCR (0.1 mg/kg, i.p.), and the treatments were continued for 14 consecutive days. Four groups were received modafinil (5, 25 and 50 mg/kg, i.p.), and gabapentin (20 mg/kg, i.p.). On the other hand, six neuropathic groups were received modafinil (5, 25 and 50 mg/kg); gabapentin (20 mg/kg); combination of modafinil (5 and 50 mg/kg) and gabapentin (20 mg/kg, i.p.). To evaluate the sensory and motor neuropathy, tail-flick and von Frey filament tests were performed, and motor nerve conduction velocity (MNCV) and excitation of nerve conduction were measured. The transient receptor potential cation channel ankyrin 1 (TRPA1), the transient receptor potential vanilloid-1 (TRPV1) and N-Methyl-D-aspartic acid (NMDA) proteins were detected in the dorsal root ganglion (DRG). Further, the DRG levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were assessed. Results: In VCR-treated rats, tail flick and von Frey latencies were significantly decreased, MNCV and excitation of the sciatic nerve significantly decreased. Pretreatment with modafinil at dose of 50 mg/kg, strongly diminished TNF-α and IL-1β levels, and prevented mixed sensory-motor neuropathy. Conclusion: Modafinil significantly improved behavioral, electrophysiological, and pathological changes. Further, combination of modafinil and gabapentin markedly improved the effect of gabapentin. As a result, modafinil might be a neuroprotective agent in prevention of VCR-induced neuropathy, which may be mediated at least in part via TRPA1 receptors.کلیدواژه ها
Peripheral neuropathy; vincristine; modafinil; gabapentin; DRG neurons; TRPA1, TRPV1, NMDA; TNF-α; IL-1βمقالات مرتبط جدید
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