Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid activity

Bobylev, A. G.; Корнев, А. Б.; Bobyleva, L. G.; Shpagina, M. D.; Фадеева, И. С.; Фадеев, Р. С.; Deryabin, D. G.; Balzarini, Jan; Troshin, Pavel A.; Podlubnaya, Z. A.

doi:10.1039/c1ob05067b

Cited by 56 publications

(45 citation statements)

References 27 publications

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“…22 Assuming these time frames are similar in humans, C60 fullerene may not benefit envenomations resulting in extremely rapid death, but it could provide therapeutic potential for the sizeable percentage of snakebite cases in which the patient survives beyond these times. With a half-life of 48 22 but further study will be needed to confirm its safety in humans.…”

Section: Discussionmentioning

confidence: 96%

C<SUB>60</SUB> Fullerenes as a Novel Treatment for Poisoning and Envenomation: A Proof-of-Concept Study for Snakebite

Darryl¹,

Hyun²,

William³

2016

j nanosci nanotechnol

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Millions of poisonings and envenomations occur annually worldwide. When treatments for these conditions exist, they are often highly specific and may be costly or unavailable, especially in remote regions and developing countries. In cases of snake envenomation, mortality and severe morbidity occur in hundreds of thousands of cases annually. These tragic physiological sequelae result from the complex mixtures of protein toxins comprising snake venom. The current gold standard for snakebite treatment is to use a mixture of polyclonal antibodies, referred to as antivenom. While effective, antivenoms have severe limitations: they are costly to produce and distribute; they must be delivered in an acute care facility; they have a relatively short shelf life; and they often induce side effects that are generally mild but occasionally serious. Certain nanoparticles, in contrast, possess protein-binding and pharmacokinetic properties that make them a potentially low-cost and readily available adjunct or alternative to antivenom for treatment of systemically distributed toxins. We therefore conducted a proof-of-concept study to test the ability of C60 fullerene to neutralize rattlesnake venom in a cricket model. We injected approximate LD 50 doses of southern Pacific rattlesnake (Crotalus oreganus helleri) venom into crickets (Acheta domesticus). In the first of two experiments, crickets injected with C60 fullerene prior to envenomation experienced 15.7% and 25.0% higher rates of survival at 24 and 48 hr, respectively, compared to control crickets. In the second experiment, survival analysis confirmed that crickets protected with C60, regardless of C60 dose (1, 2, or 4 g/g cricket mass), experienced greater survival up to 60 hr and survived significantly longer than controls. C60 fullerene conferred significant protection against rattlesnake envenomation in a cricket model. Accordingly, C60 fullerene merits further consideration as a simple, low-cost treatment for snakebite and potentially many other forms of poisoning and envenomation.

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Section: Discussionmentioning

confidence: 96%

C<SUB>60</SUB> Fullerenes as a Novel Treatment for Poisoning and Envenomation: A Proof-of-Concept Study for Snakebite

Darryl¹,

Hyun²,

William³

2016

j nanosci nanotechnol

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“…Earlier we have shown that fullerene C 60 and a number of its derivatives are capable of destroying amyloid fibrils of brain Aβ(1-42) peptide, participat ing in the pathogenesis of Alzheimer's disease, and also muscle X protein [17][18][19][20][21]. From the obtained results a conclusion has been made that fullerene C 60 and its derivatives may be regarded as potential anti amyloid preparations.…”

Section: Introductionmentioning

confidence: 83%

“…It has been shown that 1,2 (dimethoxymeth ano)fullerene is capable of inhibiting early stages of aggregation of Aβ(1-40) and Aβ (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) peptides of the brain, specifically binding with the central hydro phobic motif KLVFF (Lys Leu Val Phe Phe) of Aβ peptides [16].…”

Section: Introductionmentioning

confidence: 99%

Interaction of C60 fullerene-polyvinylpyrrolidone complex and brain Aβ(1–42)-peptide in vitro

et al. 2014

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Using a spectrophotometric method, changes occurring in solution containing brain Aβ(1-42) peptide, fullerene C 60 , and polyvinylpyrrolidone were analyzed. Using the Bent-French method, relative binding constants of fullerene C 60 with Aβ(1-42) peptide and polyvinylpyrrolidone with Aβ(1-42) peptide were determined. These data suggest that Aβ(1-42) peptide interacting with the C 60 fullerene-polyvinylpyr rolidone complex partially displaces polyvinylpyrrolidone and generates a new three molecular compound.

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“…This protective effect was observed both at early stage (day 14) of Аβ25-35-induced neurotoxicity and much later, on day 45. Fullerenes are well known to be characterized by their powerfully expressed antioxidant and antiamyloid activities [10], [11], [58], [59], [60]. Recently, we have shown that intrahippocampal injection of C60HyFn was able to protect both the mechanisms of peptide synthesis and amyloid accumulation, and CA1 neurons in rats from neurotoxic effects of the intracerebral injection of Аβ25-35 [17].…”

Section: Discussionmentioning

confidence: 99%

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats

Gordon

Podolski

Макарова

et al. 2017

JAD

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Please note: Changes made as a result of publishing processes such as copy-editing, formatting and page numbers may not be reflected in this version. For the definitive version of this publication, please refer to the published source. You are advised to consult the publisher's version if you wish to cite this paper.This version is being made available in accordance with publisher policies. See http://orca.cf.ac.uk/policies.html for usage policies. Copyright and moral rights for publications made available in ORCA are retained by the copyright holders. known to play a key role in learning and memory mechanisms, it is as yet unclear how its structures are involved in the EC pathology. In this study, changes in memory and neuronal morphology in male Wistar rats intrahippocampally injected with Аβ25-35 were correlated on days 14 and 45 after the injection to reveal specific cognitive -structural associations. The main focus was on the dentate gyrus (DG) and hippocampal areas of CA1 and CA3 because of their involvement in afferent flows from EC to the hippocampus through tri-synaptic (EC  DG  CA3  CA1) and/or mono-synaptic (EC  CA1) pathways. Evident memory impairments were observed at both time points after Аβ25-35 injection. However, on day 14, populations of morphological intact neurons were decreased in CA3 and, drastically, in CA1, and the DG supramedial bundle was significantly damaged. On day 45, this bundle largely and СА1 neurons partially recovered, whereas CA3 neurons remained damaged. We suggest that Аβ25-35 primarily affects the tri-synaptic pathway, destroying the granular cells in the DG supramedial area and neurons in CA3 and, through the Schaffer collaterals, in CA1.Intrahippocampal pretreatment with hydrated fullerene С60 allows the neurons and their connections to survive the amyloidosis, thus supporting the memory mechanisms.

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Fullerenolates: metallated polyhydroxylated fullerenes with potent anti-amyloid activity

Cited by 56 publications

References 27 publications

C<SUB>60</SUB> Fullerenes as a Novel Treatment for Poisoning and Envenomation: A Proof-of-Concept Study for Snakebite

C<SUB>60</SUB> Fullerenes as a Novel Treatment for Poisoning and Envenomation: A Proof-of-Concept Study for Snakebite

Interaction of C60 fullerene-polyvinylpyrrolidone complex and brain Aβ(1–42)-peptide in vitro

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats

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