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mechanisms

Mechanisms


In this section we provide a slightly technical overview of the various mechanisms that C60 has to offer.


Antioxidant


freeradical2.jpg Free radicals are neutralized when an antioxidant atom/molecule rebalances any unpaired electrons. Many anti-oxidants are only capable of neutralizing one free radical and they then become ineffective.

C60 can with relative ease, add up to 6 electrons. Neutralizing the radical is done by either adding or removing an electron. C60 can easily re-acquire electrons and acts as a reservoir to neutralize free radicals.

As a anti-oxidant, C60 has been measured to be 172 times more powerful than vitamin C ref.


Oxidant Reduction


Possible Mechanisms of Fullerene C60 Antioxidant Action

Computer simulations were used to demonstrate that up to 6 protons (hydrogen atoms) can be absorbed into a core of a C60 molecule. With 1 or 2 absorbed protons there in no net charge, with 3 to 6 protons a net positive charge is formed.

In the earlier theory discussion, the concept of the electron transport chain being the primary source of free radicals was introduced. This paper discusses how positively charged C60 molecules can position within mitochondria membranes and reduce the potential across the membrane. This small (10 to 15%) reduction in the gradient potential can result in a 10 fold decrease in ROS production.

C60 is not only an effective anti-oxidant, it also acts to reduce the amount of ROS in the body.

This highlights a synergistic relationship between C60 and hydrogen. A closer look at Hydrogen is provided in the next section.


Heavy Metal Detox


Mercury has 2 electrons in its outer shell, if removed we get a +2 oxidation state.

C60 reduces the bio-availability of mercury in aqueous solutions

This article discusses a research where C60 interaction with mercury was explored. It was suggested that C60 attaches to Hg making it nontoxic. It was found that the bio-availability of mercury Hg2+ decreases with increased C60 dosage, reaction time and pH level.

C60 may also attach to +1 charged non-organic metal atoms. Some additional experimental research would be required to confirm which metals and charge states this mechanism applies to.


Immune System


C60's most important contributions to the immune system include …

  • improved intra-cell signaling
  • T helper cell shift from Th2 to Th1
  • inhibition of IgE antibodies (decreased allergic hypersensitivity)

Nerd Alert … the terminology can become a bit daunting should your read on.

Applications of Anti/Prooxidant Fullerenes in Nanomedicine along with Fullerenes Influence on the Immune System

This study offers the following summary (based ref 1 and ref 2). Please note that it is inconclusive if the antibody generated response is due to the fullerene particle or the conjugated carrier protein.

immunesystem2.jpg

Response of the cells of innate and adaptive immune system to fullerene.

The cells of the innate immune system are the first to respond.
When they encounter the intruder, they become activated and start producing different cytokines, which have direct antiviral activity (IFN-𝛾, TNF-𝛼), deliver stimulatory signals to other cells of the innate system (IL-12, IL-18), initiate inflammation (IL-1𝛼/𝛽, IL-6), or act as chemoattractants that recruit inflammatory cells to the site of infection (MIP-1𝛼, IP-10).

During this cascade of events, the antigens are presented to T cells, mainly by DC, which are the professional antigen presenting cells that link the innate and adaptive immune system.

When primed, T cells secrete IL-2, which induces their clonal proliferation and development of effector functions.

Differentiated effector cells, particularly CD8+ T cells, tackle infection and eliminate the virus.
B cells can be activated by cells of innate immunity (IL-21) or directly by antigens, and upon activation they differentiate into plasma cells producing antigen specific antibodies.


A Novel Treatment of Neuroinflammation against Low Back Pain by Soluble Fullerol Nanoparticles

This research proposes that there may be two pathways by which fullerol C60 prevents cellular inflammation. The first is by a direct elimination of excess ROS. The second is by promoting anti-oxidative enzyme expression through proper signalling pathways. C60 fullerol was found to reduce TNF-α / IL-6 / COX-2 signaling and to promote cellular anti-oxidants SOD2 and CAT.

Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis

C60 aggregates (80-100 nm size / ~1 g/l ) were administered subcutaneously and epicutaneously. A significant suppression of IgE and Th2 cytokine production (IL-4 and IL-5) and a concomitant rise in Th1 cytokine production (IL-12 [EC only] and IFN-γ) was observed.

Effect of buckminsterfullerenes on cells of the innate and adaptive immune system: an in vitro study with human peripheral blood mononuclear cells

This study investigates the effect of polyhydroxy-C60 and N-ethyl-polyamino-C60 on blood mononuclear cells. This research effort observed …
No influence on T cell reactivity (no enhanced expression CD69 or production of T cell cytokines and CD4/CD8 ratio was unaffected). Activation of innate immune system cells via enhance IL-6 and CD69 expression (which may be related to macrophages or dendritic cells along with NK cells). Fullerenes only influenced naive cells (ie, cells that have not been cocultured with anti-gens activating TH1 or TH2 cells or macrophages). Incubation of human mast cells and blood basophils with fullerenes led to a significant inhibition of IgE dependent mediator release.

Stem Cells


Stem cells are generic starter cells that can divide without limit to form more stem cells or can differentiate into specific cell types. They serve as the starting point in the repair system that replenishes adult tissues. As we age, stem cells decrease in number and tend to lose the ability to differentiate.

figure2_lg.jpg

Figure illustrating the various stem cell types. Stem Cell Basics IV

Mesenchymal stem cells have been reported to be present in many tissues. Those from bone marrow give rise to a variety of cell types: bone, cartilage, fat, and stromal cells that support blood formation.

Antioxidative fullerol promotes osteogenesis of human adipose-derived stem cells

In this study, the C60 derivative fullerol, was found to increase FoxO1 and decrease ROS. FoxO1 is a transcription factor that regulates gene expression in many cell processes. The combination appears to have a modulatory effect on osteoblast differentiation of mesenchymal stem cells.


Photodynamic


photodynamic.jpg
Photodynamic therapy with fullerenes in vivo: reality or a dream?

C60 is capable of being both an anti-oxidant and an oxidant. In order for to act as an oxidant it must be stimulated by light.

The above figure illustrates the process. Incident light photons (specific frequencies of light) excite electrons to a higher energy orbital state. These excited electrons will then return to there base state and release the gained energy. This energy is released as heat, another light photon or by a transfer to another atom. When C60 is in the presence of oxygen, a free radical or a singlet oxygen will form.

C60 appears to posses a number of the properties that make it an ideal photosensitizing agent. As such, it can be used in cancer and antimicrobial therapy.


Ordered Water


orderedwater.jpg

Andrievsky et al. discuss a mechanism where C60 (and derivatives) can act as scavengers of ROS in aqueous solutions.

They showed that C60 can inactivate hydroxyl radicals by action of the ordered water coat surrounding the fullerene nano-particle. In this model hydroxyl radicals can be slowed or trapped in the water jacket long enough to allow for 2 radicals to interact and form a less reactive hydrogen peroxide molecule.


Telomeres


Telomeres are the end caps that form on the end of chromosomes. These end caps protect chromosomes from deterioration and from linking with neighbor DNA. They are made up of a repetitive nucleotide sequence having up up to 2500 copies in humans.



During replication, enzymes are not able to duplicate all the way to the end of the chromosomes. Over time the telomere length will shorten and will eventually expose the DNA strand.

When the telomere length becomes too short the cell will no longer continue to divide. At that point, the cell may become senescent or undergo apoptosis. If a cell becomes senescent, there is increased probability of impaired immune function and cancer.


Rumors have it that C60 in oil can increase telomere length. Several vendors have discussed customer feedback where measurements were taken before and after C60 consumption. Evidence so far is anecdotal and our team of expert researchers is searching for some published evidence.

Hmm .. actually these are Canadian mice and they may have wondered over to the cannabis testing lab last night. They may be trying to find there way back home.

Wikipedia - Telomere


mechanisms.txt · Last modified: 2019/04/09 11:19 by dkwk