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 C60 fullerene is a nontoxic nanomaterial, which exhibits antioxidant and cytoprotective properties. However, the precise molecular mechanism with which the C60 nanoparticle exerts cytoprotective effect in diabetic subjects has not yet been fully addressed. Thus, this study aimed to determine whether C60 fullerene prevents oxidative stress impairment and to explore the effects of C60 fullerene on apoptosis and autophagy in diabetes mellitus to clarify its potential mechanisms. These effects have been examined for olive oil extracted C60 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 C60 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, C60 fullerene ameliorated the LC3I/II ratio and prevented extremely increased autophagy flux. Contrarily, pristine C60 fullerene had no modulatory effect on all studied apoptotic and autophagy markers in non-diabetic groups. Therefore, oil extracted C60 fullerene exhibits cytoprotective effect in hyperglycemia-stressed hippocampal cells. The presented results confirm that pristine C60 fullerene nanoparticles can protect hippocampal cells against hyperglycemic stress via anti-oxidant, anti-apoptotic effects and amelioration of autophagy flux. Moreover, C60 fullerene regulates a balance of autophagy via BCL-2/Beclin-1 reciprocal expression that could prevent functional disturbances in hippocampus.

中文翻译：

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原始的C60富勒烯纳米颗粒可通过调节细胞凋亡和自噬通量来改善高血糖引起的干扰。

糖尿病是一种常见的代谢紊乱，与多种并发症相关，包括神经病，记忆力减退和认知能力下降。尽管关于糖尿病并发症的研究已有很长的历史，但尚无有效的糖尿病神经保护治疗策略。高血糖引起的程序性细胞死亡失衡可能导致神经组织细胞活力下降。取决于类型和表面特征，各种纳米材料可以诱导细胞死亡或细胞存活。原始的C60富勒烯是一种无毒的纳米材料，具有抗氧化和细胞保护特性。但是，C60纳米颗粒在糖尿病受试者中发挥细胞保护作用的确切分子机制尚未得到充分解决。从而，这项研究旨在确定C60富勒烯是否可以预防氧化应激损伤，并探讨C60富勒烯对糖尿病细胞凋亡和自噬的影响，以阐明其潜在机制。对于STZ糖尿病大鼠海马上的橄榄油提取的C60富勒烯，已经检查了这些作用。在STZ-糖尿病大鼠的大脑中观察到Caspase-3，Beclin-1的上调和氧化应激指数以及Bcl-2的下调。通过调节Caspase-3，Bcl-2，Beclin-1和LC3I / II含量，暴露于C60富勒烯12周可改善氧化还原失衡，高血糖引起的细胞凋亡和自噬通量。此外，C60富勒烯改善了LC3I / II比，并阻止了自噬通量的极大增加。相反，原始C60富勒烯对非糖尿病组中所有研究的凋亡和自噬标记物均无调节作用。因此，油提取的C60富勒烯在高血糖应激的海马细胞中表现出细胞保护作用。提出的结果证实，原始的C60富勒烯纳米颗粒可通过抗氧化剂，抗凋亡作用和自噬通量的改善来保护海马细胞抵抗高血糖应激。此外，C60富勒烯通过BCL-2 / Beclin-1相互表达调节自噬的平衡，从而防止海马功能紊乱。提出的结果证实，原始的C60富勒烯纳米颗粒可通过抗氧化剂，抗凋亡作用和自噬通量的改善来保护海马细胞抵抗高血糖应激。此外，C60富勒烯通过BCL-2 / Beclin-1相互表达调节自噬的平衡，从而防止海马功能紊乱。提出的结果证实，原始的C60富勒烯纳米颗粒可以通过抗氧化剂，抗凋亡作用和自噬通量的改善来保护海马细胞免受高血糖的压力。此外，C60富勒烯通过BCL-2 / Beclin-1相互表达调节自噬的平衡，从而防止海马功能紊乱。