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.
Highlights
Parkinson's disease (PD) is most prevalent in older people (>65 y. o.), but in inherited cases it can begin in age 30–40 y. o. (Williams-Gray, 2016)
C60 fullerene aqueous solution (C60FAS) treatment increased the number of tyrosine hydroxylase (TH)-positive cells with Q = 3.7 ± 0.5 vs. the sham-lesioned group (P < 0.05), this parameter did not return to control values (Fig. 2b)
C60 fullerene treatment induced a mild shift in antioxidant-prooxidant system in the brain of 6-OHDA-PD rats vs. saline treated rats, with more profound negative effect on the glutathione system, which might be the sign of its toxic effect
Summary
Parkinson's disease (PD) is most prevalent in older people (>65 y. o.), but in inherited cases it can begin in age 30–40 y. o. (Williams-Gray, 2016). The main feature of PD pathogenesis is a loss of dopaminergic neurons in the substantia nigra (SN) with the deposition of intraneuronal aggregates of α-synuclein (Lewy bodies) (Siderowf & Lang, 2012). It is observed in up to 66% of all PD-patients thereby effecting psychological and social distress and reducing quality of life (Carrasco et al, 2018) and related to disordered central nervous system (Stocchi & Torti, 2017). The pathomechanism of delayed colonic transit in PD relates to a disordered central nervous system as well as age-related loss of excitatory cholinergic neurons in the colon and impaired cholinergic function (Amani et al, 2017; Ferreira et al, 2018). The PD treatment is complicated (Pirtošek et al, 2020)
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