Global Inhibition of Reactive Oxygen Species ROS Inhibits Paclitaxel-Induced Painful Peripheral NeuropathyReport as inadecuate




Global Inhibition of Reactive Oxygen Species ROS Inhibits Paclitaxel-Induced Painful Peripheral Neuropathy - Download this document for free, or read online. Document in PDF available to download.

Paclitaxel Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain intraperitoneal 2 mg-kg paclitaxel on days 0, 2, 4 and 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl TEMPOL were compared. Systemic 100 mg-kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg-kg PBN days −1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg-kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose 250 mg-kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g and 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg-kg TEMPOL day −1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals alone.



Author: Mehmet Fidanboylu, Lisa A. Griffiths, Sarah J. L. Flatters

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents