Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats

Abstract

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.