Abstract:
Paclitaxel (Taxol®), an effective anti-neoplastic agent in the treatment of several solid tumors, produces a peripheral neuropathy with sensory predominance as one of its toxic side effects. Little is known regarding the mechanisms underlying this complication. Mitogen-activated protein kinases (MAPKs), a family of serine- threonine specfic kinase comprised of extracellular signal regulated kinase (ERK), c- Jun NH;-terminal kinase (INK) and p38 kinase, have been shown to be activated in neuronal and other cell types in response to paclitaxel. Therefore, this work was aimed to study the activity of all three subfamilies of MAPKs in primary sensory neurons and glial cells in the animal model of paclitaxel-induced neuropathy. Adult male Wistar rats were given a weekly intraperitoneal injection of 16 mg/kg paclitaxel (P group) or vehicle (Cremophorrethanol, V group) for 5 consecutive weeks and were subjected to quantitative sensory tests and nerve conduction velocity (NCV) study. Prolonged reaction time to the heat at the tail and hind paw including reduced tail NCV was observed, indicating the neuropathy. Subsequently, the animals were sacrficed and L4~5 dorsal root ganglia (DRG) were removed for Western blot analysis. The immunoblots showed an insignficant increase in the phosphorylation of ERK in the DRG of paclitaxel-treated rats compared with those of the controls. Similarly, an insignficant activation of p38 was demonstrated in the V and P groups relative to the controls. For JNK, comparable levels of phosphorylation in all groups were observed. It cannot be concluded that there is no change in the activity of MAPKs in DRG in response to paclitaxel until further studies in various time points are completed.
