Today in the western universe one of the prima causes of decease is malignant neoplastic disease ( WHO Media Centre, 2010 ) . To get down off with I will cite some facts. One in every three people worldwide will develop some signifier of malignant neoplastic disease during their life-time and in the UK 1 in every four people die due to malignant neoplastic disease. In the twelvemonth 2007 there were merely under 300,000 new instances of malignant neoplastic disease diagnosed in the UK entirely
As wellness attention professionals we would be really interested in happening ways to handle and forestall malignant neoplastic disease, as this would take to a longer and better quality of life for the patient.
Cancer is a name given when an unnatural cell grows out of control. The cell is said to be immortal as it does non follow the normal way of programmed cell decease ( programmed cell death ) . Cancer normally start of in a peculiar country it can easy distribute to neighboring cells and to other variety meats throughout the organic structure.
Due to the facts mentioned it would be a great benefit to mankind to be able to handle, remedy or even prevent malignant neoplastic disease. Cancer itself is non caused by a individual cause but is multifactorial. There are many theories as to what causes malignant neoplastic disease but one that I am traveling to look into is the free extremist theory of malignant neoplastic disease.
Free Radical Theory
Free groups are molecules or atoms that contain odd negatrons and therefore are unstable and really reactive. There are many ways which free groups can be produced in the organic structure but most of them are produced as a byproduct of respiration ( Fang, 2002 ) .
During respiration stairss glycolysis, link reaction and the Krebs rhythm, reduced NAD and FAD are produced. The decreased coenzymes pass through negatron conveyance ironss where they are oxidised and the byproducts are hydrogen atoms. The H atom is so split to bring forth an negatron and a proton. The proton goes onto aid bring forth ATP ( energy ) which is the terminal required consequence of respiration ( Baker, 2007 ) .
After ATP has been produced the negatrons are accepted by O along with the protons to bring forth H2O. For every O acceptor molecule ( O ) , four negatrons and four protons are required to bring forth two molecules of H2O. As shown below
However is non ever the instance. Sometimes the negatrons leak prematurely onto the O before the protons arrive, which produces free groups such as superoxide, H peroxide and besides hydroxyl groups depending on the figure of negatrons that are leaked ( as shown below ) .
There are many types of free groups, but in the organic structure the 1s we are most interested in are superoxides, hydroxyl, peroxyl groups and non groups such as H peroxide ( Yan, 2006 ) . As the free groups mentioned have oxygen at its Centre they are known as reactive O species ( ROS ) .
Other than this free extremist intermediate H peroxide is produced in the thyroid secretory organ in order to bring forth tetraiodothyronine. Hydrogen peroxide Acts of the Apostless as a accelerator in the reaction which involves attaching I to thyroglobulins.
Superoxide in the organic structure is non ever a bad thing as scavenger cells produce superoxide ‘s utilizing NADPH Oxidase ( enzyme ) , which is used to kill pathogens occupying the organic structure.
Oxidative emphasis can do malignant neoplastic disease ( Gate, 1999 ) . Oxidative emphasis can be categorised as endogenous and/or exogenic. We will foremost see endogenous.
Free groups are thought to do malignant neoplastic disease, redness, disease and old age but before I go into that I must explicate the mechanism as to how they upset the natural order of the organic structure.
As stated antecedently free groups are extremely unstable and reactive and they will seek to brace every bit shortly as possible by stealing an negatron from someplace. This could intend that that if a hydroxyl extremist were to come in contact with a cell wall which is made from a phospholipids bi-layer it would seek and steal and electron from it. As an negatron is removed from the lipoid cell wall the cell wall becomes the extremist, and the image below shows how it finally go lipid peroxidise, which would falsify the original bilayer construction.
( Vickers, 2007 )
Lipid peroxide formation means the cell wall is damaged which leads to cell wall escape and the terminal consequence of lipid peroxides may even be carcinogenic ( Marnett, 1999 )
Another state of affairs can happen when free groups can damage the Deoxyribonucleic acid itself ( Aust, 1999 ) which may non needfully kill the cell but the free extremist interacting with DNA may change the Deoxyribonucleic acid reproduction or cause mutants and bring forth unnatural proteins which in bend causes malignant neoplastic disease ( Dreher, 1996 ) ( Valco, 2004 ) ( Nakab, 2006 ) .
Mutants themselves can be permutation, add-on or omission, and can ensue in inactivation of tumor suppresser cistrons ( Couples, 2000 ) .
Free groups are usually at a province of homeostasis in the organic structure when produced reasonably. The free groups green goodss are used for many physiological procedures as mentioned before and besides for vascular tone ( NO ) – ( Dr, 2002 ) .
Exogenous oxidative emphasis can originate from many external environmental causes such as smoke, pollution, ionizing radiation and UV light etc.
Cigerettes contain pitch which contains free groups such as quinine and hydroquinone. The free groups in the pitch are capable of cut downing O to bring forth superoxide taking to hydroxyl groups and we already know what they are capable of making in the organic structure ( Church, 1985 ) .
Pollution in the ambiance has broken down the ozone bed which has allowed harmful UV visible radiation to come through. UV light hitting the tegument can bring forth free groups such as hydroxyl which cause DNA harm taking to malignant neoplastic disease ( Autier, 1995 )
Ionizing radiation straight move on the organic structure such as alpha ( from the interior ) , beta and gamma ( from the exterior ) radiation. They straight ionise the atoms in the organic structure bring forthing free groups, which can finally do malignant neoplastic disease.
Inflammation is besides a known to bring forth free groups under oxidative emphasis. Oxidative emphasis can trip written text factors which lead to an addition in cistron look of certain cytokines. This may subsequently do chronic redness which based on experimental informations is known to do malignant neoplastic disease ( Reuter, 2010 ) .
The diagram below summarised free extremist production of course and via oxidative emphasis.
Antioxidant Activity Test
As discussed antecedently antioxidants work as free extremist scavengers. In order to compare different antioxidant and to see which works better we must hold agencies to compare them.
There are a figure of ways in which we can mensurate the capacity of antioxidants, they include Oxygen Radical Absorbance Capacity ( ORAC ) , 2,2-azino-bis ( 3-ethylbenzthiazoline-6-sulphonic acid ( ABTS ) and 2,2-diphenyl-1-picrylhydrazyl ( DPPH ) assay. The most normally used method is utilizing the DPPH check ( Sharma and Bhat, 2009 )
DPPH is a stable free group with an odd negatron on the outer shell of the N atom. Antioxidants can be used to seek and scavenge the free groups and the consequences can be found utilizing one of two methods. The first method is by utilizing of electron paramagnetic resonance ( EPR ) which measures the spin of atoms, the 2nd is by mensurating optical optical density of DPPH between 515nm – 520nm ( largely around 517nm ) UV Spectroscopy. The One I will concentrate on is the UV Spectroscopy method.
I will now briefly discourse how DPPH is produced for usage.
DPPH comes in crystal signifier, and a stock solution is produced by blending DPPH into methyl alcohol and buffer The DPPH solution produced is deep violet in coloring material, but when the free groups become neutralized it becomes pale yellow in coloring material. As we can see the coloring material alterations that occur with DPPH that tells us it occurs within the seeable spectrum which is between 390nm and 750nm ( O dependance ) , so if we ran a scan of DPPH utilizing this spectrum it should give a peak optical density at around 517nm. The ground we measure optical density is because from it we are happening out the alteration in concentration as per the Beer Lambert Law which is optical density is straight relative to concentration. This makes sense when we add the antioxidant to DPPH it get down cut downing the free extremist concentration which will be shown by a decrease in optical density. Now the better the antioxidant and its ability to scavenge free groups the lower the optical density will go. To fix the antioxidant it is dissolved in the same medium as DPPH ( methyl alcohol and buffer ) on molar footing with DPPH, but is made more concentrated ( usually 10 times the strength of DPPH solution ) . This is done so we can add the minimal volume of antioxidant to the DPPH solution so the DPPH solution does non go dilute as this would cut down the optical density, therefore the concentration, before we even start the experiment which would spit our consequences ( Sharma, 2009 ) .
Now that we are able to state by what extent different antioxidant cut down DPPH we need to be able to compare them against each other and against what other people have produced. This is done by utilizing a mention criterion, to which all antioxidant activity can be compared to and in the field the criterion that is used is Trolox ( soluble vitamin E Derivative ) . The difference between the standard soaking up of DPPH and with Trolox is compared to the differences produced by other antioxidant compounds, and the better the antioxidant the higher the numerical value of difference, comparative to Trolox ( Re, 1999 ) .
Other things to observe about DPPH is that although it is a stable free extremist it can be affected by visible radiation and heat so care must be taken that it is stored in a cold and dark environment such as a deep-freeze. Due to the methyl alcohol in DPPH it should n’t stop dead but should remain absolutely preserved giving accurate consequences every clip. DPPH is besides affected by pH that is why we add buffer to the DPPH stock solution, to guarantee stable pH ( Sharma, 2009 ) .
When free groups are usually produced, natural antioxidant enzymes such as superoxide dismutase and glutathione peroxidise catalase mop them up in the organic structure. This leads to a homeostatic balance in the organic structure. Now when the balance is overturned and free groups are produced at a faster rate than they can be eliminated due to oxidative emphasis, we get extra free groups being produced in the organic structure. Below is a image of how natural antioxidants eliminate free groups in the organic structure.
( Racila, 2009 )
From the above image we can state that antioxidants scavenge free groups. As discussed antecedently extra free groups can do malignant neoplastic disease, so if we could extinguish and neutralize the extra free groups in the organic structure it would be a move back towards the homeostasis of free groups in the organic structure.
Glutathione is sometimes called the ‘master antioxidant ‘ in the organic structure. The ground for this is that in most instances it is glutathione that reduces the major free groups produced in the organic structure. Glutathione has other functions other than merely an antioxidant.
Its other functions include possible mending DNA which may hold been damaged when it came into contact with free groups ( Pujari, 2009 ) .
It makes the immune system stronger by increasing the sum of T cells and natural slayer cells produced ( Chang, 2002 )
It regulates the azotic oxide rhythm ( Ha, 1999 )
Through direct junction it detoxifies xenobiotics and carcinogens ( Wadleigh, 1988 ) .
Our organic structure besides produces other natural antioxidants such as Ubiquinol which is a natural lipoid soluble antioxidant, made in most cells ( Jezek, 2005 ) . Blood plasma contains uric acid, and uric acid is known as a potent cut downing agent and antioxidant ( Maxwell, 1997 )
Other than our ain of course produced antioxidants we can derive a batch of antioxidants by holding the right diet. By eating the right workss we can derive antioxidants such as vitamin C and E.
One of the chief groups of natural antioxidants are the flavonoids. Flavonoids are powerful antioxidants found in nutrient such as workss and veggies and besides in bewerages such as vino, beer and tea ( Ishige, 2001 ) .
As explained antecedently flavonoid is an umbrella term but underneath it there are many different phenoplast compounds which are categorised by their construction which include flavones, flavonols, flavanones, isoflavones, anthocyanidins, catechins and chalcones. Other than flavonoids antioxidant affects, other benefits of flavonoids include antiviral, anti-allergic, anti-platelet, anti-inflammatory, and antitumor activities ( Buhler, 2000 ) .
Flavonoids differ in construction to each other because differences in construction consequence in differences in activity. A popular structural alteration done to flavonoids to alter its activity is altering the figure and place of hydroxy or methoxyl groups. It is the hydroxyl or methoxyl group that provide the negatrons for antioxidant effects but more does n’t needfully intend better. Research has shown that by attaching 3 hydroxy groups to flavonoid it consequences in an addition in activity while if 5 or 7 hydroxyl groups are added it increases cytotoxicity. As for methoxyl it has shown to give good consequences with 3 or 5 groups but shown cytotoxicity with 6 groups attached ( Jeong, 2007 ) ( Heim, 2002 ) ( Rice-Evans, 1996 ) .
There are other possible mechanisms by which flavonoids show possible for malignant neoplastic disease direction other than merely as antioxidants
Anti oestrogenic mechanisms – by competitively suppressing the oestrogen receptor ( Burt, 2001 ) .
Anti proliferation mechanism – this is done by bring oning programmed cell death of malignant neoplastic disease cell and halting the cell rhythm and growing of the cell by working at the chekpoints G2/M and G1/S ( Simoni, 2006 ) ( Lee, 2004 ) ( Burt, 2001 ) .
As stated antecedently by detoxification, Immune responce and DNA fix
From the different type of flavonoids the 1s I am most interested in are the stilbene ‘s and the chalcones.
Stilbenes such as Resveratrol have been used in carnal tests, already and showed a batch of promise. In animate being proving where it showed supplementation of Resveratrol were given it prevented mice from acquiring skin malignant neoplastic disease when carcinogens were introduced into them ( Jang, 1997 ) . On another juncture when Resveratrol given to mice orally at a dosage of 1mg/kg it reduced the size and figure of the tumor which had formed in the gorge ( Li, 2002 ) . Another survey looking into Resveratrol and its derived functions and showed there effects on malignant neoplastic disease cells ( HL60 leukemia ) . The survey concluded that a certain derived function they called 6b induced programmed cell death, and it looked assuring for future research ( Simoni, 2006 ) .
The 2nd flavonoid group of flavonoids I will look at are chalcones.
Chalcones are flavonoids that lack a C ring. There has been research done into chalcones but non a great trade, but new involvement has been shown to these compounds as the possible benefits of chalcones are coming to visible radiation.
A survey was conducted where chalcone sydnone-substitution took topographic point. The ensuing chalcones were found to be cytotoxic to tumour cells and reduced the activity and size of the tumor. Some of the chalcones were besides found to suppress lipid peroxide and were able to wipe up up free groups such as superoxides and hydroxyl groups. The consequences besides showed an interesting find that the ability of the derived functions to stamp down tumour growing was non dependent on merely the antioxidant activity, which would intend that there are potentially other mechanisms at work other than merely free extremist moping ( Ruby, 1994 ) .
A different survey was done into chalcones and there antioxidant belongingss. The consequences showed that the man-made chalcones they produced were reasonably good antioxidants but were really good at suppressing hydroperoxide ( Gacche, 2008 ) .
More late a comparatively new compound Garcinol has been isolated. It is a really powerful antioxidant and really powerful anticancer compound. It has besides shown to suppress NF-kB which is a protein that controls written text in DNA. NF-kB is known to be rather active in malignant neoplastic disease cells and is known as a possible site of action when it comes to commanding malignant neoplastic disease, as suppression of NF-kB is shown to cut down proliferation of malignant neoplastic disease cells. NF-kB degrees addition under oxidative emphasis, so by wipe uping up free groups in the atomic country Garcinol has shown to be a really interesting curative drug ( Padhye, 2009 ) .
Cancer today is one of the biggest slayers. We know that antioxidants are known to stamp down tumour growing, and based on past surveies that have already been conducted, we know that more research is needs to be done in this country as the possible chances look assuring. Due to this I will be further researching the antioxidant affects of different chalcones, as I believe they have the possible to salvage 1000000s of lives.