Neuroprotective effect of the carnosine - α-lipoic acid nanomicellar complex in a model of early-stage Parkinson's disease

Regul Toxicol Pharmacol. 2018 Jun;95:254-259. doi: 10.1016/j.yrtph.2018.03.025. Epub 2018 Mar 28.

Abstract

In a model of early-stage Parkinson's disease induced by a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Wistar rats, a neuroprotective effect of a new derivative of carnosine and α-lipoic acid (C/LA nanomicellar complex) was demonstrated. Acute intraperitoneal administration of carnosine, α-lipoic acid and C/LA complex following MPTP administration normalized the total antioxidant activity in the brain tissue. Of all the compounds tested only C/LA complex normalized the metabolism of dopamine (DA) and serotonin (5-HT), while its components did not show similar effects when used separately. C/LA complex effectively restored the level of DA metabolites: the level of DOPAC was increased by 24.7 ± 5.6% compared to the animals that had received MPTP only, and the level of HVA was restored to the values observed in the intact animals. Integral metabolic indices of DA (DOPAC/DA and HVA/DA ratios) and 5-HT turnover (5-HIAA/5-HT ratio) in the striatum tended to increase in case of C/LA complex administration.

Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Carnosine; Catecholamines; Lipid peroxidation; Nanomicellar complex of carnosine and α-lipoic acid; Neuroprotection; Parkinson's disease; Rat; α-lipoic acid.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Brain / drug effects
  • Brain / metabolism
  • Carnosine / pharmacology
  • Carnosine / therapeutic use*
  • Dopamine / metabolism
  • Homovanillic Acid / metabolism
  • Male
  • Micelles
  • Nanoparticles / therapeutic use*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Rats, Wistar
  • Serotonin / metabolism
  • Thioctic Acid / pharmacology
  • Thioctic Acid / therapeutic use*

Substances

  • Antioxidants
  • Micelles
  • Neuroprotective Agents
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Thioctic Acid
  • Carnosine
  • Dopamine
  • Homovanillic Acid