Riboflavin And Pyridoxine Restore Dopamine Levels And Reduce ...

The main incident in neurological disorders is excitotoxicity which entails an extensive upsurge in the concentrations of intracellular Ca2+ and the production of reactive species such as ROS and RNS by lethal pathways [1]. In addition, there are alterations of the mitochondrial ultrastructure and DNA damage caused by nitric oxide- (NO-) dependent oxidative stress [2]. This damage is the primary event in 3-nitropropionic acid (3-NPA) toxicity.

In Wistar rats, it has been reported that 3-nitropropionic acid leads to neurodegeneration and that the intravenous administration in rats provides valuable insight of Huntington’s disease model [3]. There is evidence that metabolism of transmitter dopamine by monoamine oxidase enzyme may promote striatal damage in mitochondrial toxin induced models of Huntington’s disease (HD) [4], and that HD is a devastating neurodegenerative disorder that reflect neuronal dysfunction and ultimately death in selected brain regions with striatum and cerebral cortex being the principal targets [5]. Some nutrients are known to act as antioxidants; and although neglected as an antioxidant, riboflavin is one of such nutrients that independently or as a component of the glutathione redox cycle has an important antioxidant action [6]. On the other hand, pyridoxine alters serotonin metabolism [7]. Both compounds are water-soluble vitamins that possess antioxidant activity [8].

Neuromodulation activity of the NO- is a documented fact, however, an excess amount of it can produce oxidative damage or nitroso-glutathione (NOGSH) inside the cell, thus; causing the damage of the cell [9]. It is known that free radicals (FR) induce damage to the components of the cell [10]. Such FR-induced damage particularly affects the plasma membrane lipids [11]. In addition, the cells of the central nervous system are extremely susceptible to these unpaired electron molecular species. Nitric oxide (NO) acts on hypothalamic neurocircuits and on higher brain circuits, e.g. dopaminergic system to regulate energy and glucose homeostasis [12]. Therefore, the presence of FR may upset this regulatory function of NO. The structural proteins in the lipid bilayer are contiguous with brain plasma membrane phospholipids [13] and the ionic inflow and outflow through the lipid bilayer is maintained by Na+, K+ ATPase enzyme which stimulates Na+ and K+ flows [14]. It is know that when the activity of the enzyme Na+, K+ ATPase is inhibited, it triggers the release of excitatory amino acid in the CNS [15].

In view of all the aforementioned, the objective of the present work was to make a comparative analysis of the protective effects derivable from riboflavin (B2) and pyridoxine (B6) on 5-HIAA and dopamine levels, as well as on selected markers of oxidative stress in rats’ brain regions after an induction of Huntington’s disease (HD). Literature reports suggest that these substances may participate in the neutralization of excess free radicals in oxidation mechanisms. The production of free radicals, a usual biological phenomenon, is regulated by different metabolic routes, which constitute the first line of defence in the human body.

The aim of this work was to determine if riboflavin (B2) and pyridoxine (B6) provide protection to the brain against free radicals generated by 3-nitropropionic acid (3-NPA) by measuring the levels of dopamine (DA) and selected oxidative stress markers.