Protective effects of phosphatidylcholine on oxaliplatin-induced neuropathy in rats

Life Sci. 2015 Jun 1:130:81-7. doi: 10.1016/j.lfs.2015.03.013. Epub 2015 Mar 25.

Abstract

Aims: The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on oxaliplatin-induced peripheral neuropathy.

Main methods: Male Sprague-Dawley rats were randomly divided into three groups: the control group, the oxaliplatin group (4mg/kg, twice per week for 4weeks) and the oxaliplatin+PC (300mg/kg) group. To evaluate the effect of PC, we examined the thermal nociceptive threshold changes in oxaliplatin-induced peripheral neuropathy by conducting paw pressure, hot-plate and tail-flick tests. Additional experiments on the degree of oxidative stress in the sciatic nerves were performed by measuring the level of MDA, total glutathione (GSH), glutathione peroxidase (GPx) activity and superoxide dismutase (SOD) activity. We also used histopathological and immunohistochemical methods to observe neuronal damage and glial activation.

Key findings: PC attenuated oxidative stress by increasing antioxidant levels. In histopathological evaluation, the PC administrated group maintained normal morphologic appearance of sciatic nerves, similar to the control group. In spinal cords, however, no significant difference between the oxaliplatin-alone group and the oxaliplatin+PC group was observed. In the immunohistochemical evaluation, PC administration ameliorated oxaliplatin-induced microglial activation.

Significance: It is suggested that PC has a therapeutic potential against oxaliplatin-induced peripheral neuropathy due to its antioxidant property and modulation of microglial activities.

Keywords: Microglial activation; Oxaliplatin; Oxidative stress; Peripheral neuropathy; Phosphatidylcholine (PC).

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Disease Models, Animal
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Neurotoxicity Syndromes / etiology*
  • Organoplatinum Compounds / toxicity*
  • Oxaliplatin
  • Oxidative Stress / drug effects
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / prevention & control*
  • Phosphatidylcholines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Organoplatinum Compounds
  • Phosphatidylcholines
  • Oxaliplatin