The protective effects of aripiprazole on vincristine - induced peripheral neuropathy in a rat model

Abstract

Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been limited due to its peripheral neuropathy toxicity. Aripiprazole, which is an antipsychotic agent is a partial agonist the dopaminergic D2 receptor (D2R) and the serotonin 5-HT1A and 5-HT7 receptors Several studies have shown that aripiprazole exerts neuroprotective and immunomodulatory properties. This study aimed to investigate the effects of aripiprazole on brain injury in a rat model. Male Wistar rats were intraperitoneally injected with VCR and normal saline four times per week for 2 weeks. In the treatment group, aripiprazole (3 mg/kg) was administered intraperitoneally 30 min prior to VCR injection every day. Mortality rate, weight variations and histopathological changes were monitored. Hot plate, tail flick, von fery and motor nerve conduction velocity (MNCV) tests were used to evaluate sensory and motor neuropathy. Levels of nNOS and iNOS were assessed by enzyme-linked immunosorbent assay (ELISA). Moreover, the protein levels of caspase-3, p65 nuclear factor kappa B (NF-<kappa>B) and phospho-p65 NF-<kappa>B in the dorsal ganglion root were examined by Western blot analysis. Co-administration of aripiprazole with VCR significantly reversed alterations in the hot plate, tail flick threshold, von frey and sciatic MNCV induced by VCR and also prevented mixed sensory-motor neuropathy, as indicated by better general conditions, behavioral and electrophysiological results. In addition, aripiprazole improved the body weight loss caused by VCR. The levels of iNOS and nNOS were significantly diminished in the treatment group. These findings were confirmed by western blot and histopathological analysis. In conclusion, this study demonstrated that aripiprazole significantly attenuated VCR-induced neuropathy and could be considered as a neuroprotective agent to prevent the VCR-induced neuropathy.