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C60 derivatives attenuate neuroinflammatory response; an in vitro study

c60 in vitro

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#1 malbecman

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Posted 16 June 2015 - 06:04 PM


 Interesting new paper.    It specifically looks at a COOH derivative of C60 but does look at its effects on inflammation & mitochondria.

 

 

 

Nanoscale Res Lett. 2015 Dec;10(1):953. doi: 10.1186/s11671-015-0953-9. Epub 2015 May 30.

Carboxylic Acid Fullerene (C60) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics.
 
 
Abstract

Fullerene (C60) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C60 derivatives (C60-COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C60-COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (ΔΨm) were also significantly inhibited by C60-COOH. Moreover, we also found that C60-COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C60 derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C60 derivatives. 

PMID:

26058514

 

 Provisional open-access PDF is here:

 

http://www.nanoscale.../1/246/abstract

 

 

 

 

 


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#2 bixbyte

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Posted 18 June 2015 - 01:45 PM

I read this study and thought about why the C60 was treated to hold a single COOH molecule and thought is THIS a method to make C60 more aqueous?

Does the carboxyl chain improve the efficacy of C60 or is it a way to add more water?

And there were some older studies using C60 -- COOH

This would take away two negative charges from the C60. I do not know if that is a good thing or a bad thing.

Plus from the view of the Sigma Aldrich diagram of the molecule does the COOH actually look this way?

I think the COOH is dispersing over the molecule sort of like in a certain pattern.

I would believe since C60 possesses properties of the Alkene nature.

 

Look at this model of C60 -- COOH. I do not believe this is valid. If we consider that C60 is negatively and this a limited reaction to disperse

only a single molecule of COOH per C60.

The structure is wrong as the orbitals must follow a certain pathway.

This molecule is a new science that needs to be viewed at an atomic level.

  

http://www.sigmaaldr...13323-large.png

 

(Just some thoughts, opinions and key highlights of this study in my most humble opinion)

 

 

 

selected parts of this study:

Results obtained from MTT assays showed that C60-COOH up to 100 μM for 24 h was well tolerated by BV-2 cells without any influence on cell viability 

 
BV-2 cells pretreated with C60-COOH exhibited less mitochondrial fragmentation compared with LPS-stimulated cells, which suggested that C60-COOH represent a novel inhibitor of mitochondrial fragmentation.
 
Emerging evidence has linked mitochondrial dysfunction such as mitochondria fission to a variety of oxidative stress-related diseases, including neurodegenerative diseases and cancer [37]. The results shown above indicate that C60-COOH prevented LPS-induced increased mitochondrial fragmentation and expression of mitochondrial fission proteins. Excessive mitochondria fission events are normally associated with ROS generation and mitochondria dysfunction [32]. Therefore, we determined mitochondrial ROS level and mitochondrial membrane potential (ΔΨm) as parameters of mitochondrial fission in BV-2 cells, which were incubated with LPS with or without C60-COOH pretreatment by flow cytometry using MitoSOX, respectively. The results showed that the pretreatment with C60-COOH suppressed the LPSmediated mitochondrial ROS generation (Fig. 5a, b) and mitochondria membrane depolarization (Fig. 5c, d). This may be attributed to the antioxidant properties of C60-COOH as reported earlier [10, 14]. Radical-scavenging abilities of C60 derivatives have been attributed to the molecular properties, including large electron affinity and formation of electron-deficient areas on the C60, and these properties of C60 derivatives may lead to direct ROS scavenging similar to that catalyzed by superoxide dismutase (SOD) [10, 14]. In addition, water-soluble C60 derivatives such as polyhydroxylated C60 (C60-OH) have also been reported to induce phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), γ- glutamate cysteine ligase (γ-GCS), and NAD(P)H: quinine oxidoreductase 1 (NQO-1), to attenuate oxidative stress-induced apoptosis [11]. Further studies are needed to elucidate the molecular mechanisms of C60-COOH to combat the deleterious action of ROS.
 

 



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#3 Nuke

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Posted 18 June 2015 - 06:51 PM

I have a feeling that people experiment with C60 derivatives instead of C60 because they can patent the derivatives, but not C60.


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#4 Kalliste

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Posted 19 June 2015 - 08:48 PM

Sarah Vaugther has a blurb about that on her site. They want to play with stuff that can generate money later perhaps. I guess that sounds reasonable.


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#5 niner

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Posted 20 June 2015 - 01:55 PM

People look at analogs because naked c60 is a very biologically intractable compound.  If you ever hope to get a compound onto the market, then you have to have an IP position; that's "the system".  It does sometimes happen that academics will do science for the sake of understanding, without expecting to become a billionaire.  There was a time when almost all academic science was like that.


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#6 Walter Derzko

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Posted 07 July 2015 - 12:36 AM

> I have a feeling that people experiment with C60 derivatives instead of C60 because they can patent the derivatives, but not C60.

The water soluble version of C60 called Carbon 60 Hydrated Fullerene is patent pending in the USA

Dr. Grigoriy Andrievsky's American patent application for C[60] Hydrated Fullerenes http://www.freepaten...14/0079746.html
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#7 Turnbuckle

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Posted 13 August 2015 - 02:42 AM

I have a feeling that people experiment with C60 derivatives instead of C60 because they can patent the derivatives, but not C60.

 

 

You have to precisely define what you're claiming in a patent, especially as C60 and dissolved C60 are already known. Besides, C60 by itself will likely not get into the mitochondria, while C60 dissolved in EVOO likely has a witche's brew of adducts, and some will be a lot better than others for longevity and for other uses. Some may actually be harmful. For instance, the epoxides that form as the oil gets old.







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