Sunday, September 23, 2012

More on Nanoparticles causing DNA damage from MOM hips throught oxidatve stress (4 of x in a series)

Next in the series (4 of x) I will discuss the the key systemic processes in these journal articles:

Redox chemistry,
Free Radicals and
ROS (Reactive oxygen species)
Oxidative stress

Prior posts in the sequence
1 of x
More on Nanoparticles causing DNA damage from MOM hips with oxidative stress ( 1 of x in a series)
2 of x
3 of x

Discussing the first of 4 seminal works on the issues related to causing free radicals in the cell environment from MoM.

This article was published in 2007.  Effect of nano-and micron-sized particles of cobalt-chromium alloy on the human fibroblasts in vitro.  (see the prior posts for definitions.)

1.  Nano particles induce more DNA damage than Micron particles.

2. Nano particles disintegrate within the cells faster than micro particles  that crease electron dense deposits in the cell that were enriched in cobalt.

3.  The concept of Nanotoxicology is a key concept for understanding what materials should go into the further design of hips.

4.  Nanotoxicology is the study of the internal exposure to particles from surgical implants

5.  Metal on metal produce smaller particles than metal on poly and in fact there are more metal on metal particles generated than poly.

6.  Both implants may cause an increase of chromosome aberrations in patients.

7.  The wear debris from implants may cause  DNA and chromosome damage, cytokine release and cytoxicity in human cells.

In 2007, this study by the top scientists in the field  decided to compare the biologic effects of the same Co and CR alloy used in the hip implants when presented to human fibroblasts in tissue cultures.  so the investigators wanted to know what happens when you subject metal on metal to  cells in the  body.

[A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen,[1] the structural framework (stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals]

Here is what they found:

(1) They found the generation of free radicals by the particles such that they could see the presence of hydrogen peroxide suggesting that a fenton driven reaction was taking place actually generating these free radicals. 

(The hydroxyl radical can damage virtually all types of macromolecules: carbohydrates, nucleic acids (mutations), lipids (lipid peroxidation) and amino acids  The hydroxyl radical has a very short in vivo half-life of approximately 10−9 seconds and a high reactivity.[3] This makes it a very dangerous compound to the organism.[4][5]

Unlike superoxide, which can be detoxified by superoxide dismutase, the hydroxyl radical cannot be eliminated by an enzymatic reaction. Mechanisms for scavenging peroxyl radicals for the protection of cellular structures includes endogenous antioxidants such as melatonin and glutathione, and dietary antioxidants such as mannitol and vitamin E.

(2)  ROS was measured so see the prior posts for that definition

(3)  Genotoxcity/ test results showed DNA damage to the DNA via a break in single and double strands in a dose dependent manner.

(4)  Cytoxicity/ The cellular integrity was measured and after 3 days of exposure and the level of LDH was measured and was found to be significant.

(5)  Cytokine release (Adverse effects of cytokines have been linked to many disease states and conditions ranging from major depression[12] and Alzheimer's disease[13] to cancer[14] with levels either being elevated or changed.)

(6)  This increased biological reactivity could be due to one or more  of the following:
  • increased release of free radicals within the cell with subsequent oxidative DNA damage
  • increased release of metals from the nanoparticles
(7)  Exposure of the cells to nanoparticles and micron sized particles cause different types and amount of cell damage.

(8)  There was a faster and shorter release of metal from the nanoparticles.

(9)  The nanoparticles caused more mitorchodrial damage, more DNA damage and more subsequent cell death than the microparticles (poly)

(10)  The oxidative damage to DNA by Hydroxly free radicals occurred.

(11)  There may have been additional and secondary damage in the nanoparticle exposed cells from increased damage to mitochondria proteins or from lipid peroxidation which could have generated a number of secondary DNA damaging agents in the cells.

There may be a number of fundamentally different biological responsies of human cells to surgical implant materials which depend on particle size.

Next in the series, we will look at DNA damage across the cell barrier. (5 of x)

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