An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice

Cent Nerv Syst Agents Med Chem. 2020;20(1):13-25. doi: 10.2174/1871524920666200120142508.

Abstract

Background: Parkinsonism is a neurodegenerative disorder with a heavy disease burden, despite the discovery and application of drugs. Current research is beginning to suggest the possible crucial roles of micronutrients such as pyridoxal phosphate in the prevention or management of neurodegenerative disorders.

Objective: We investigated the possible protective effects of supplemental pyridoxal phosphate in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice.

Methods: Mice were assigned to eight groups of 30 mice each. Groups included Vehicle control (fed standard diet (SD), and administered intraperitoneal {ip} injection of saline and saline per orem), levodopa-carbidopa (LD) group (SD, saline ip and LD per orem), two groups fed pyridoxal phosphate-supplemented diet (at 100 and 200 mg/kg of feed), and administered saline both ip and orally, CPZ group (SD, CPZ ip and saline per orem), CPZ/LD group (SD, CPZ ip and LD per orem) and finally two groups fed pyridoxal phosphate -supplemented diet (at 100 and 200 mg/kg of feed) and administered CPZ ip plus saline per orem. Treatments were administered daily for a period of 21 days to allow for the induction of Parkinsonism features. Body weight and food intake were measured weekly while neurobehavioural and biochemical tests were assessed at the end of the experimental period.

Results: Pyridoxal phosphate supplementation was associated with a reduction in CPZ-induced suppression of open-field horizontal locomotion and rearing; and a significant increase in grooming activity. Administration of pyridoxal phosphate-supplemented diet was also associated with improvements in working-memory in CPZ-treated mice; and there was reduction in the index of anxiety and catalepsy score.

Conclusion: Pyridoxal phosphate supplementation was associated with significant benefits in CPZ-induced Parkinsonism-like changes in mice.

Keywords: Dopamine; micronutrients; neurobehaviour; neurodegenerative disease; neurotransmitter; vitamins..

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antiparkinson Agents / therapeutic use
  • Antipsychotic Agents*
  • Behavior, Animal / drug effects
  • Body Weight / drug effects
  • Carbidopa
  • Chlorpromazine*
  • Diet
  • Drug Combinations
  • Eating / drug effects
  • Grooming / drug effects
  • Levodopa
  • Lipid Peroxidation / drug effects
  • Mice
  • Motor Activity / drug effects
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / drug therapy*
  • Pyridoxal Phosphate / therapeutic use*

Substances

  • Antioxidants
  • Antiparkinson Agents
  • Antipsychotic Agents
  • Drug Combinations
  • carbidopa, levodopa drug combination
  • Levodopa
  • Pyridoxal Phosphate
  • Carbidopa
  • Chlorpromazine