C₆₀ Fullerene Prevents Restraint Stress‐Induced Oxidative Disorders in Rat Tissues: Possible Involvement of the Nrf2/ARE‐Antioxidant Pathway

Abstract

The effects of C60FAS (50 and 500 μg/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N-acetylcysteine. Oxidative stress biomarkers (ROS, O2·−, H2O2, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, γ-GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH-related enzymes γ-GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis. Under a stress condition, C60FAS attenuates ROS generation and O2·− and H2O2 releases and thus decreases lipid peroxidation as well as increases rat tissue antioxidant capacity. We have shown that C60FAS supplementation has dose-dependent and tissue-specific effects. C60FAS strengthened the antiradical defense through the upregulation of MnSOD in brain cells and maintained MnSOD protein content at the control level in the myocardium. Moreover, C60FAS enhanced the GSH level and the activity/protein expression of GSH-related enzymes. Correlation of these changes with Nrf2 protein content suggests that under stress exposure, along with other mechanisms, the Nrf2/ARE-antioxidant pathway may be involved in regulation of glutathione homeostasis. In our study, in an in vivo model, when C60FAS (50 and 500 μg/kg) was applied alone, no significant changes in Nrf2 protein expression as well as in activity/protein levels of MnSOD and GSH-related enzymes in both tissues types were observed. All these facts allow us to assume that in the in vivo model, C60FAS affects on the brain and heart endogenous antioxidative statuses only during the oxidative stress condition.

Water-Soluble Pristine C60 Fullerenes Inhibit Liver Fibrotic Alteration and Prevent Liver Cirrhosis in Rats

“…Since water-soluble nanoscale pristine C 60 fullerenes are powerful antioxidants [56,57], presumably, their ability to scavenge free radicals is one of the main mechanisms for 9 Oxidative Medicine and Cellular Longevity providing antifibrotic activity. Indeed, the main three pathways responsible for liver fibrogenesis are growth arrestspecific gene 6 serum protein (Gas6)/Axl, transforming growth factor β (TGF-β)/Smad, and Wnt signaling [4], and all of them have been shown to be upregulated by ROS.…”

Nonel approaches to correction of mitochondrial dysfunction and oxidative disorders in Parkinson’s disease

“…Due to their hydrophilic properties and the ability to scavenge free radicals, fullerenols may, in the future, provide a serious alternative to the currently used pharmacological agents in chemotherapy, treatment of neurodegenerative diseases, and radiobiology. Water-soluble derivatives of fullerenes (fullerenols and malonic acid derivatives) scavenge ROS more efficiently than conventional antioxidants [101][102][103][104][105][106]. Therefore, hydrophilic fullerene derivatives are promising candidates for the use as neuroprotective and antioxidant agents, as confirmed in electrophysiological studies indicating that two fullerene derivatives (C60(OH)12 and C60 (OH)18-20O3-7) showed excellent antioxidant properties (confirmed by electron paramagnetic resonance).…”

Activation of the Cold and Menthol Receptor TRPM8 Improves Post-Traumatic Recovery of Rat Muscle Soleus During Fullerene Treatment

“…Ãлавную роль в инициации воспалительных реакций играет каскадное, прогрессирующее увеличение свободнорадикальных компонентов. Способность С 60 -фуллерена эффективно нейтрализовать свободные радикалы [1][2][3][22][23][24], по нашему мнению, является основной причиной полученных позитивных результатов применённой терапии.…”