Sevda Shayesteh1,2, Mina Khalilzadeh2, Nasrin Takzaree3, Ahmad Reza Dehpour4,5. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Anatomy and Medicinal Plants Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. dehpoura@sina.tums.ac.ir. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. dehpoura@sina.tums.ac.ir.
Abstract
BACKGROUND: Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases. OBJECTIVES: Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN. METHODS: VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays. RESULTS: VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve. CONCLUSION: This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.
BACKGROUND: Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases. OBJECTIVES: Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN. METHODS: VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays. RESULTS: VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve. CONCLUSION: This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.
Authors: Suzan Williams; Paula MacDonald; James D Hoyer; Ronald Duncan Barr; Uma Harish Athale Journal: Pediatr Blood Cancer Date: 2005-01 Impact factor: 3.167