C60 Fullerene Reduces 3-Nitropropionic Acid-Induced Oxidative Stress Disorders and Mitochondrial Dysfunction in Rats by Modulation of p53, Bcl-2 and Nrf2 Targeted Proteins

Abstract

C60 fullerene as a potent free radical scavenger and antioxidant could be a beneficial means for neurodegenerative disease prevention or cure. The aim of the study was to define the effects of C60 administration on mitochondrial dysfunction and oxidative stress disorders in a 3-nitropropionic acid (3-NPA)-induced rat model of Huntington’s disease. Animals received 3-NPA (30 mg/kg i.p.) once a day for 3 consecutive days. C60 was applied at a dose of 0.5 mg/kg of body weight, i.p. daily over 5 days before (C60 pre-treatment) and after 3-NPA exposure (C60 post-treatment). Oxidative stress biomarkers, the activity of respiratory chain enzymes, the level of antioxidant defense, and pro- and antiapoptotic markers were analyzed in the brain and skeletal muscle mitochondria. The nuclear and cytosol Nrf2 protein expression, protein level of MnSOD, γ-glutamate-cysteine ligase (γ-GCLC), and glutathione-S-transferase (GSTP) as Nrf2 targets were evaluated. Our results indicated that C60 can prevent 3-NPA-induced mitochondrial dysfunction through the restoring of mitochondrial complexes’ enzyme activity, ROS scavenging, modulating of pro/antioxidant balance and GSH/GSSG ratio, as well as inhibition of mitochondria-dependent apoptosis through the limitation of p53 mitochondrial translocation and increase in Bcl-2 protein expression. C60 improved mitochondrial protection by strengthening the endogenous glutathione system via glutathione biosynthesis by up-regulating Nrf2 nuclear accumulation as well as GCLC and GSTP protein level.

The Residual Effect of C60 Fullerene on Biomechanical and Biochemical Markers of the Muscle Soleus Fatigue Development in Rats

“…Against this background, the use of C 60 fullerenes can enhance and promote further activation of the above processes. This is proved by our preliminary studies, which confirmed the fact that the use of C 60 fullerene under extreme conditions affects the rapid formation of adaptive reactions of the body by affecting such transcription factors as Nrf2 (NF-E2-related factor 2), NF-κB, and p53 [44]. The glutathione system plays an important role in the implementation of antiradical and antiperoxide cell protection [22].…”

Nrf2 Pathway in Huntington’s Disease (HD): What Is Its Role?

“…Fullerene C60 (an allotrope of carbon) neutralizes ROS and possesses a SOD-like activity [ 137 ], making it a suitable compound for preventing oxidative stress [ 138 , 139 ]. In 3-NP treated male rat Wistar model of HD, pre- and post-treatment with C60 prevented mitochondrial dysfunction and enhanced nuclear Nrf2 protein expression in the brain [ 140 ].…”

Cerebrolysin administration counteracts elevated oxidative stress in blood of patients with Parkinson’s disease

“…It was also established that administration of CBL prevented the decline in Bcl-2 protein concentration in rat striatum induced by rotenone [10]. It is known that expression of antiapoptotic protein Bcl-2 is modulated by oxidative stress: enhanced OS and altered level of antioxidants occurred in the brains of Bcl-2 -deficient mice [29] as well as at acute 3-nitropropionic acid intoxication [3]. So, one of the mechanisms through which CBL counteracts elevated OS in PD could be regulation of Bcl-2 protein expression in neuronal cells.…”

“…Increased ROS generation and impaired antioxidant defense could both contribute to OS development in neurodegenerative disorders [2,3]. Oxidative damage may contribute to the aggregation of protein into brain structures such as Lewy bodies which form the key histological hallmark of the second most prevalent neurodegenerative disease worldwide -Parkinson's disease (PD) [2].…”