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    Pristine C-60 Fullerene Nanoparticles Ameliorate Hyperglycemia-Induced Disturbances via Modulation of Apoptosis and Autophagy Flux
    (Springer/Plenum Publishers, 2020) Demir, Ersin; Nedzvetsky, Viktor S.; Agca, Can Ali; Kirici, Mahinur
    Diabetes mellitus is a prevalent metabolic disorder associated with multiple complications including neuropathy, memory loss and cognitive decline. Despite a long history of studies on diabetic complications, there are no effective therapeutic strategies for neuroprotection in diabetes. Hyperglycemia-induced imbalance in programmed cell death could initiate a decline in neural tissue cells viability. Various nanomaterials can induce either cell death or cell survival dependent on the type and surface features. Pristine C(60)fullerene is a nontoxic nanomaterial, which exhibits antioxidant and cytoprotective properties. However, the precise molecular mechanism with which the C(60)nanoparticle exerts cytoprotective effect in diabetic subjects has not yet been fully addressed. Thus, this study aimed to determine whether C(60)fullerene prevents oxidative stress impairment and to explore the effects of C(60)fullerene on apoptosis and autophagy in diabetes mellitus to clarify its potential mechanisms. These effects have been examined for olive oil extracted C(60)fullerene on the hippocampus of STZ diabetic rats. Up-regulation of Caspase-3, Beclin-1 and oxidative stress indexes and down-regulation of Bcl-2 were observed in the brain of STZ-diabetic rats. The exposure to C(60)fullerene for a period of 12 weeks ameliorate redox imbalance, hyperglycemia-induced disturbances in apoptosis and autophagy flux via modulation of Caspase-3, Bcl-2, Beclin-1 and LC3I/II contents. Furthermore, C(60)fullerene ameliorated the LC3I/II ratio and prevented extremely increased autophagy flux. Contrarily, pristine C(60)fullerene had no modulatory effect on all studied apoptotic and autophagy markers in non-diabetic groups. Therefore, oil extracted C(60)fullerene exhibits cytoprotective effect in hyperglycemia-stressed hippocampal cells. The presented results confirm that pristine C(60)fullerene nanoparticles can protect hippocampal cells against hyperglycemic stress via anti-oxidant, anti-apoptotic effects and amelioration of autophagy flux. Moreover, C(60)fullerene regulates a balance of autophagy via BCL-2/Beclin-1 reciprocal expression that could prevent functional disturbances in hippocampus.