The effect of water-soluble pristine C60 fullerene on 6-OHDA-induced Parkinson’s disease in rats

Abstract

Oxidative stress is thought to be one of the mechanisms that leads to the dysfunction and degeneration of dopaminergic neurons in Parkinson’s disease pathogenesis and presumed to be underway during the prodromal phase. Therefore, therapy, which is effective against pre-motor symptoms, might be effective in preventing or delaying the development and progression of Parkinson’s disease. The aim of our study was to investigate the therapeutic efficiency of pristine C60 fullerene aqueous solution (C60FAS) during Parkinson’s disease in rats. The unilateral dopamine deficiency was induced in male Wistar rats (220–250 g) by stereotaxic microinjection of neurotoxin 6-hydroxydopamine (6-OHDA, 12 μg). C60FAS was injected to rats intraperitoneally daily for 10 days (0.65 mg/kg per day). The percentage of destroyed dopaminergic neurons was determined by the apomorphine test and by IHC staining of tyrosine hydroxylase-positive neurons in substantia nigra. We evaluated the rat body weight, the water and food intake, Open Field behavioural test, the level of biochemical antioxidant system, the activity of peritoneal macrophages. Levels of spontaneous and carbachol-stimulated colon motility were estimated by ballonographic method in vivo. C60FAS showed a positive tendency to increase the number of tyrosine hydroxylase-positive cells in the midbrain, which was associated with more profound improvement in apomorphine-rotation behaviour and slight relief of the anxiety level in Open Field test. Furthermore, C60FAS treatment increased the index of stimulated distal colon motor activity while it did not have a significant effect on water content in feces and total gastrointestinal transit time. C60FAS treatment did not affect water intake behaviour or body weight changes while it induced an increase of glutathione level and decrease activity of glutathione peroxidase in the brain as well as an increase in activity of peritoneal macrophages in 6-OHDA-Parkinson’s disease rats. These findings confirmed the potential therapeutic effectiveness of water-soluble pristine C60 fullerene in Parkinson’s disease pathogenesis, though there is ground for caution because of its systemic mild toxic effect.

Changes in the expression of TRPV4 and TRPM8 channels in the colon of rats with 6-OHDA-induced Parkinson’s disease

“…The dopamine neurons were disrupted by unilateral stereotaxic microinjections of 12 μg of selective neurotoxin 6-OHDA (Sigma, USA) in the medial forebrain bundle. The sham-lesioned groups of ani-mals were injected with 4 μl 0.9% NaCl as described in more detail previously [14]. In brief, 6-OHDA was dissolved in 4.0 μl of NaCl with the addition of 0.1% ascorbic acid (as a stabilizer inhibiting oxidation of 6-OHDA).…”

“…Starting at 120 min post-gavage, rats were monitored every 10 min for the production of a red fecal pellet. Total GI transit time was considered as the interval between T 0 and the time of the first observance of carmine red in stool [14].…”

“…In our previous study [14] we used a rat model of easily reproducible partial lesion of the nigrostriatal system (unilateral injection of 6-hydroxydopamine (6-OHDA) and showed reduced spontaneous and carbachol-stimulated colon motor activity in it. Moreover, pharmacological activation of TRPV4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of colon smooth muscle cells in the PD rats model [15].…”