14 replies to this topic

[geo12the]

FYI:

 

J Biomed Nanotechnol. 2014 Aug;10(8):1610-9.

Modulation of gene expression of adenosine and metabotropic glutamate receptors in rat's neuronal cells exposed to L-glutamate and [60]fullerene.

Giust D, Da Ros T, Martín M, Albasanz JL.

Abstract

L-Glutamate (L-Glu) has been often associated not only to fundamental physiological roles, as learning and memory, but also to neuronal cell death and the genesis and development of important neurodegenerative diseases. Herein we studied the variation in the adenosine and metabotropic glutamate receptors expression induced by L-Glu treatment in rat's cortical neurons. The possibility to have structural alteration of the cells induced by L-Glu (100 nM, 1 and 10 microM) has been addressed, studying the modulation of microtubule associated protein-2 (MAP-2) and neurofilament heavy polypeptide (NEFH), natively associated proteins to the dendritic shape maintenance. Results showed that the proposed treatments were not destabilizing the cells, so the L-Glu concentrations were acceptable to investigate fluctuation in receptors expression, which were studied by RT-PCR. Interestingly, C60 fullerene derivative t3ss elicited a protective effect against glutamate toxicity, as demonstrated by MTT assay. In addition, t3ss compound exerted a different effect on the adenosine and metabotropic glutamate receptors analyzed. Interestingly, A(2A) and mGlu1 mRNAs were significantly decreased in conditions were t3ss neuroprotected cortical neurons from L-Glu toxicity. In summary, t3ss protects neurons from glutamate toxicity in a process that appears to be associated with the modulation of the gene expression of adenosine and metabotropic glutamate receptors.

 

[niner]

What do they mean by fullerene derivative t3ss? T3ss normally refers to the Type 3 Secretion System, a bacterial protein complex. Hard to say what to make of this without the full text.

[hav]

Here's another paper by some of the same folks that describes what they dub t3ss:

 

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells

 

 

C₆₀ fullerene hydrosoluble bis-adduct isomer trans-3 (T3SS)

 

... which looks like some sort of water-soluble c60/toluene compound.

 

Howard

 

[niner]

Here's another paper by some of the same folks that describes what they dub t3ss:

 

Modulation of Adenosine Receptors by [60]Fullerene Hydrosoluble Derivative in SK-N-MC Cells

 

 

C₆₀ fullerene hydrosoluble bis-adduct isomer trans-3 (T3SS)

 

 

Thanks Howard.  This compound is a tetra-cation, so it's very different from c60oo, and the results they report regarding the adenosine receptor probably have no bearing on us.  Maybe they should have written "T3SS, not to be confused with that other T3SS that has a thousand mentions in PubMed."  Or called it something else...

[Turnbuckle]

What do they mean by fullerene derivative t3ss? T3ss normally refers to the Type 3 Secretion System, a bacterial protein complex. Hard to say what to make of this without the full text.

 

 

It means trans-3 isomer.

 

 

 

Edited by Turnbuckle, 28 July 2014 - 08:12 PM.

[Kalliste]

Found this. Is it relevant to us?

Potential use of the nano-compound fullerenol for the treatment of paraquat-induced acute lung injury in rats (660.16)

 Authors

Abstract

The present work aimed at investigating the effect of fullerenol in the treatment of paraquat-induced acute lung injury (ALI). Wistar rats were separated in control, ALI and ALI+fullerenol groups. In rats given paraquat there was increase of lipid peroxidation in lung, neutrophilia, accumulation of neutrophils in lung and bronchoalveolar lavage (BAL), associated with an increase in pulmonary levels of TNF-α, IL-1β, IL-6 and CINC-1, and serum levels of TNF-α and IL-6. Histological analysis showed inflammatory infiltrate, perivascular and intra-alveolar edema, hemorrhage, vascular congestion and atelectasis. There was elevation of the basal production of nitric oxide (NO) and hyporesponsiveness of the aorta to vasoconstrictors. Treatment with fullerenol normalized lipid peroxidation, neutrophils number on BAL, lung and blood, the level of IL-1β and CINC-1 in lung, and TNF-α and IL-6 on serum. All histological parameters were normalized. Furthermore, treatment with fullerenol normalized the basal production of NO and vascular function. Finally, fullerenol increased the survival of animals with ALI. In conclusion, fullerenol combines antioxidative and antiinflammatory activities, reducing pulmonary and vascular alterations, and mortality induced by paraquat. Hence, fullerenol can be an effective and promising drug for the treatment of paraquat-induced acute lung injury.April 2014 The FASEB Journal vol. 28 no. 1 Supplement 660.16

http://m.fasebj.org/...pplement/660.16

[Kalliste]

 

  Abstract

The aim of this study was to investigate the effects of water soluble fullerene (fullerenol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerenol C₆₀(OH)_n (n: 18–22) alone and in combination with acetamiprid for 24 h. The micronucleus test, comet assay and γ-H2AX foci formation assays were used as genotoxicity endpoints. Cytotoxicity was evaluated using the clonogenic assay. The maximum tested concentration of fullerenol (1.600 μg/ml) induced 77% survival where as the lowest concentration (25 μg/ml) was not cytotoxic where as acetamiprid was cytotoxic. Fullerenol did not induce genotoxicity at tested concentrations (50–1600 μg/L). On the other hand, acetamiprid (>50 μM) significantly induced formation of micronuclei, and double and single stranded DNA breaks in IMR-90 cells. For simultaneous exposure studies, two non-cytotoxic concentrations (50 and 200 μg/ml) of fullerenol and three cytotoxic concentrations of acetamiprid (100, 200 and 400 μM) were selected. As a result, we observed that co-exposure with fullerenol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our results indicated the protective effect of water soluble fullerene particles on herbicide induced genotoxicity.

 

 

http://www.sciencedi...048357514001321

 

 

Abstract

Aim: To evaluate the effect of fullerenol on the antioxidant system of goat epididymal sperm. Methods: Fresh epididymides of adult goats were obtained from local slaughter houses and sperm were collected by chopping the epididymis in modified Ringer's phosphate solution (RPS medium). After several washings the sperm samples were equally dispersed in RPS medium and incubated with fullerenol (1, 10 and 100 mmol) and FeSO₄/ascorbate (40/200 mmol) with or without fullerenol (1, 10 and 100 mmol) for 3 h at 32. After incubation, an aliquot of sperm samples were homogenized and centrifuged and the supernatant used for biochemical studies. Results: In FeSO₄/ascorbate-incubated samples, the activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase and glutathione reductase, were decreased while lipid peroxidation increased as compared to the control sperm samples. In fullerenol-incubated sperm samples, the activities of superoxide dismutase, glutathione peroxidase and glutathione reductase were increased while lipid peroxidation was decreased in a dose-dependent manner. Co-incubation of sperm with fullerenol (1,10 and 100 mmol) and FeSO₄/ascorbate (40/200 mmol) increased the activities of antioxidant enzymes and prevented the iron-induced elevation of lipid peroxidation in a dose-dependent manner. Conclusion: Fullerenol reduces iron-induced oxidative stress in epididymal sperm of goat by increasing the activities of antioxidant enzymes and decreasing lipid peroxidation.

http://www.asiaandro...-682X/4/149.htm

 

 

Despite the convincing evidence concerning the neuroprotective properties of water-soluble fullerene derivatives, little is known about their mechanism of action and possible side effects occurring in the neural tissue. Therefore, the potential therapeutic properties of fullerenols in the treatment of neurologic diseases require further investigation.

http://www.hindawi.c...ri/2013/751913/

 

 

 

Studies on anti-tumor and antimetastatic activities of
fullerenol in a mouse breast cancer model
Carbon, Volume 48, Issue 8, July 2010, Pages 2231-2243
Fang Jiao, Ying Liu, Ying Qu, Wei Li, Guoqiang Zhou,
Cuicui Ge, Yufeng Li, Baoyun Sun, Chunying Chen
Abstract
The purpose was to examine the anti-tumor and antimetastatic
activities of fullerenol and their related mechanisms.
Thirty EMT-6 tumor-bearing mice were injected intraperitoneally
with 0.1 ml saline or 0.1 ml saline containing fullerenol C60(OH)20
(0.08 and 0.4 mg/ml) daily for 16 days.
Using tumor tissues, we investigated imbalances in the oxidative
defense system and the expression of several angiogenesis factors.
C60(OH)20 exhibits anti-tumor and antimetastatic activities in
EMT-6 breast cancer metastasis model.
Treatment with C60(OH)20 was found to modulate oxidative stress
significantly.
The expression of several angiogenesis factors was reduced in
tumor tissues after treatment with fullerenol.
Importantly, CD31 (also known as PECAM-1, platelet endothelial
cell adhesion molecule) expression and vessel density were markedly
reduced in tumors from fullerenol-treated mice compared with
controls.
Modulation of oxidative stress in tumor tissues, inhibition of the
formation of angiogenesis factors, and subsequent reduction in tumor
vessel density and the nutrient supply to tumor cells could be
important
mechanisms by which fullerenol aggregates inhibit tumor growth and
suppress carcinoma metastasis in vivo.

 

 

 

ABSTRACT

Colorectal cancer (CRC) is one of the most common cancers world-wide, with highest incidence rates in western countries. In recent years, much effort has been dedicated in search for natural or pharmacological preventive agents, which would block or attenuate CRC process. In search for new pharmacological agent, the effects of fullerenol C60(OH)24 nano particles (FNP) on liver oxidative status and promotion or progression phase of colorectal carcinogenesis in dimethylhydrazine-induced rat model of CRC were investigated. Our results demonstrate that FNP effectively inhibited formation of dysplastic aberrant crypt foci, which are regarded as early histopathological lesions in the pathogenesis of CRC. FNP treatment also improved activity of antioxidant enzymes in the liver. Since this was the first study investigating FNP effects on colon carcinogenesis further studies are needed to evaluate its protective effect also in other phases of carcinogenesis and to investigate whether its inhibitory activity was due to modulation of carcinogen-induced oxidative stress or another yet unknown anticarcinogenic activity.

http://connection.eb...azine-rat-model

 

 

Are these researchers using some fundamentally different compound?

 

 

[niner]

Are these researchers using some fundamentally different compound?

 

It's a different molecule. Fullerols have hydroxyl (-OH) groups distributed all over the cage, and are water soluble. We believe C60oo to be a fatty acid adduct. This should be pretty hydrophobic, and should be membrane soluble or incorporated into the membrane. There's a twist, though. C6O crystals are not air stable. They intercalate oxygen from the air, and that intercalated oxygen can form oxidation products with the C6O, probably epoxides. These could further react. The common production methods of c60oo do not exclude air, and are therefore creating molecules that might not be quite as hydrophobic as we first thought. Beyond that, C6O has been shown to be hydroxylated in water, so it may be forming a more fullerol-like structure in the body. Which of these oxidation routes is dominant is an open question, but I've found a biological effect that depends on air exposure in the manufacturing process. I made a batch of c60oo where I excluded air as much as was possible without a glove box. I found that this batch lost the anti-eczema effect. (I have eczema, which most c60oo eliminates, one of the reasons I like it so much.) I made a new batch, this time grinding the fullerene crystals in air, and allowing air into the reaction flask. The resulting batch cleared up my eczema in only a couple days.

The active species in the body is probably more complicated than we first imagined, but the chemistry of the various fullerene analogs is similar. They all seem to readily accept a free radical electron, for example. The biological effects of the various analogs seem to be consistent as well. Individual effects may vary in magnitude depending on the precise structure of the fullerene compound, but the fullerene itself seems to be the dominant chemotype.

[Logic]

...intercalated oxygen can form oxidation products with the C6O, probably epoxides. These could further react. The common production methods of c60oo do not exclude air, and are therefore creating molecules that might not be quite as hydrophobic as we first thought. Beyond that, C6O has been shown to be hydroxylated in water, so it may be forming a more fullerol-like structure in the body. Which of these oxidation routes is dominant is an open question, but I've found a biological effect that depends on air exposure in the manufacturing process. I made a batch of c60oo where I excluded air as much as was possible without a glove box. I found that this batch lost the anti-eczema effect. (I have eczema, which most c60oo eliminates, one of the reasons I like it so much.) I made a new batch, this time grinding the fullerene crystals in air, and allowing air into the reaction flask. The resulting batch cleared up my eczema in only a couple days.

The active species in the body is probably more complicated than we first imagined, but the chemistry of the various fullerene analogs is similar. They all seem to readily accept a free radical electron, for example. The biological effects of the various analogs seem to be consistent as well. Individual effects may vary in magnitude depending on the precise structure of the fullerene compound, but the fullerene itself seems to be the dominant chemotype.

 

 

This is very interesting info Niner!

 

Is it possible  that oxidised C60/C60oo is responsible for some or all of C60oo's effects!???

 

Perhaps the C60oo-O is what has what seems to be an anti bacterial/viral/cancer effect or some other effect?

 

[Kalliste]

The results seem very positive. Has anyone tried ingesting it that we know of? Does it occur naturally?

[niner]

Is it possible  that oxidised C60/C60oo is responsible for some or all of C60oo's effects!???

 

Perhaps the C60oo-O is what has what seems to be an anti bacterial/viral/cancer effect or some other effect?

 

Yeah, I think it is.  Not for all of c60oo's effects, but at least for the immunomodulatory effects, maybe some others.  I'm less certain about the other effects.  C60oo isn't exactly antibacterial (at least in vivo, in the absence of photons) , but it seems to reduce the likelihood of infection, probably by improving barrier function.  That would apply to both viral and bacterial infections.

[Logic]

Yeah, I think it is.  Not for all of c60oo's effects, but at least for the immunomodulatory effects, maybe some others.  I'm less certain about the other effects.  C60oo isn't exactly antibacterial (at least in vivo, in the absence of photons) , but it seems to reduce the likelihood of infection, probably by improving barrier function.  That would apply to both viral and bacterial infections.

 

 

Thx Niner

I think this is important and worthy of its own thread?
 

[Kalliste]

Maybe a moderator could split my posts regarding Fullernol into a separate topic? I thought it was C60 when I posted.

[niner]

That's ok, Cosmical.  It's starting to look like Fullerols have more in common with c60oo than we initially thought.  I think it's ok to leave them here.

[Kalliste]

Maybe we could make a topic about Fullerols with an appropriate name. I can post more links as I find them there.

I have now read about Fullerols, hydrated fullerenes and C60-oo.

My ape-brain is wired to see patterns in everything I know. But I am getting the feeling that there is something weirdly positive going on with these fullerenes.