Sunday, October 2, 2011

Oxidative stress induced cancers: Is the trivalent chromium really oxidized hexavalent chromium? (1 of x)

Note: It has been publicized that the Depuy hip contains the less toxic trivalent chromium (aka Chromium 3.)  There are quite a number of studies which I have uncovered that suggests that the trivalent chromium may be an oxidized hexavalent chromium (aka, chromium 6) which is known to have greater carcinogenic properties than the chromium 3.   I have also lerned that much of the underlying molecular damage my be due to its intracellurlare reduction to the even more highly reqacitve and short lived Chromium 3 and Chromium 5.  I hope that someone at some point can clarify the chromium 3 vs 6 issues.
I haven't seen this study below  before but I found the intro interesting but may not be directly related to the hip.  This whole issue of oxidized stress induced cancers I think is an important component of understanding the long term systemic issues related to the hip.
Definitions to understand before you read the abstract:
(1) Potassium dichromate, K2Cr2O7, is a common inorganic chemical reagent, most commonly used as an oxidizing agent in various laboratory and industrial applications. As with all hexavalent chromium compounds, it is potentially harmful to health and must be handled and disposed of appropriately. It is a crystalline ionic solid with a very bright, red-orange color. It is also known as potassium bichromate; bichromate of potash; dipotassium dichromate; dichromic acid, dipotassium salt; chromic acid, dipotassium salt; and logpizte.
(2) cytotoxicity- is the quality of being toxic to cells.
(3) genotoxicity-In genetics, genotoxicity describes a deleterious action on a cell's genetic material affecting its integrity. Genotoxic substances are known to be potentially mutagenic or carcinogenic, specifically those capable of causing genetic mutation and of contributing to the development of tumors
(4) Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of tissues can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Some reactive oxidative species can even act as messengers through a phenomenon called redox signaling.  Reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens.
(5) Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons. ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis.[1] However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically.[1] This may result in significant damage to cell structures. This cumulates into a situation known as oxidative stress
Int J Environ Res Public Health. 2009 Feb;6(2):643-53. Epub 2009 Feb 12.

Potassium dichromate induced cytotoxicity, genotoxicity and oxidative stress in human liver carcinoma (HepG2) cells.

Source

Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, CSET, Jackson State University, Jackson, MS, USA. anita.k.patlolla@jsums.edu

Abstract

Chromium is a widespread industrial waste. The soluble hexavalent chromium Cr (VI) is an environmental contaminant widely recognized to act as a carcinogen, mutagen and teratogen towards humans and animals. The fate of chromium in the environment is dependent on its oxidation state. Hexavalent chromium primarily enters the cells and undergoes metabolic reduction to trivalent chromium, resulting in the formation of reactive oxygen species together with oxidative tissue damage and a cascade of cellular events. However, the results from in vitro studies are often conflicting. The aim of this study was to develop a model to establish relationships between cytotoxicity, genotoxicity and oxidative stress, in human liver carcinoma [HepG2] cells exposed to potassium dichromate. HepG2 cells were cultured following standard protocols and exposed to various concentrations [0-50 microM] of potassium dichromate [K2Cr2O7]. Following exposure to the toxic metal, the MTT assay was performed to assess the cytotoxicity, the thiobarbituric acid test to evaluate the degree of lipid peroxidation as an indicator of oxidative stress and the alkaline comet assay was used to assess DNA damage to study genotoxicity. The results of the study indicated that potassium dichromate was cytotoxic to HepG2 cells. The LD(50) values of 8.83 +/- 0.89 microg/ml, 6.76 +/- 0.99 microg/ml, respectively, for cell mortality at 24 and 48 hrs were observed, indicating a dose- and time-dependent response with regard to the cytotoxic effects of potassium dichromate. A statistically significant increase in the concentration of malondialdehyde [MDA], an indicator of lipid peroxidation, was recorded in exposed cells [15.9 - 69.9 microM] compared to control [13 microM]. Similarly, a strong dose-response relationship (p<0.05) was also obtained with respect to potassium dichromate induced DNA damage (comet assay) in HepG2 cells exposed [3.16 +/- 0.70 - 24.84 +/- 1.86 microns - mean comet tail length]; [12.4 +/- 1.45% - 76 +/- 1.49%-% tail DNA] to potassium dichromate than control [3.07 +/- 0.26 microns--mean comet tail length]; [2.69 + 0.19%-% Tail DNA], respectively. The results demonstrated that potassium dichromate was highly cytotoxic to HepG2 cells, and its cytotoxicity seems to be mediated by oxidative stress and DNA damage.


[I will try to stay away from these highly technical abstracts however, oxidative stress is an important concept to study in this murky area of long terms systemic effects of chromium....in my opinion...again, I am not a medical person nor scientist.]

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