Oxidation Mender
Remove Free Radicals
Also Known as Oxidative Stress

Anti-tumor Activity of Black Rice Extract

The carbohydrate characteristics of rice extracts are not fully understood. Previous studies of polysaccharides from Ganoderma lucidum (Wang et al., 1997), Grifola umbellata (Miyazaki et al., 1979) and Cordyceps Ophioglossoides (Yamada et al., 1984) have shown that b-(1,3)- and a- (1,6)-D-glucan are responsible for their immunomodulating activities. However, the 1,6-a-linked glucan, isolated from rice bran and black soybean, has also been demonstrated as a stimulant of anti-tumor immunity (Takeo et al., 1988; Takeda et al., 1994).

The type of structure, polysaccharides or others, responsible for the activity of rice extracts remains to be determined. Moreover, while taken orally, carbohydrates and proteins may be digested rapidly through gut passage. Whether this digestion is beneficial to bind to gastrointestinal epithelial cells to trigger mucosal immunity, or to enter circulation to activate peripheral peripheral blood mononuclear
cel, remains to be elucidated. The potential application of rice extracts would be an adjuvant treatment in patients receiving cancer treatment. Being orally taken like food, the compliance of patients receiving rice extracts might be greater than that of current therapeutic adjuvant drugs.

In summary, stimulation of peripheral blood mononuclear cell by extracts of black rice extract both inhibits growth and induces differentiation of human leukemic cells. We are currently conducting an in vivo study using a tumor implantation model to observe the effects of these two types of rice on tumor growth and host immune responses. Hui-Fen Liao et al 2006

Anthocyanins

The active ingredients found in black rice extract are flavonoids. Flavonids of black rice are anthocyanins. The two anthocyanins are, cyanidin 3-glycoside and peonidin 3-glycoside, have been identified as the major compounds extracted from black rice (Zhang et al., 2006).

Cardiovascular Health

Clinical studies have reported a positive correlation between cardiovascular health status and consumption of black rice extracts. This particular rice possesses protective effects through many mechanisms, including antioxidant, anti-inflammatory, anti-proliferation, and lipid lowering effects.

Antioxidant properties of black rice have been found to exert not only the induction of superoxide dismutase, catalase (Chiang et al., 2006) and glutathione peroxidase activities (Auger et al., 2002), but also the suppression of reactive oxygen species (reactive oxygen species) and nitric oxide radicals in clinical and biological model systems (Hu et al., 2003).

Coronary Heart Disease

Supplementation of black rice extract has been shown to result in numerous advantages including improvement of antioxidant and anti-inflammatory status in patients with coronary heart disease, reduction of oxidative stress and inflammation (Wang et al., 2007), decrease in plasma lipid levels and alleviation of atherosclerotic lesions in animal models (Ling et al., 2002).

Human Leukemic Cells

In 2006 Hui-Fen Liao et al, demonstrated that the water extracts of Black rice moderately inhibit the growth of human leukemic cells and induce their differentiation into mature monocytes/macrophages. There are two ways for a natural product to act on leukemic cells, either by direct inhibition of cell proliferation or by stimulating the secretion of differentiation-inducing factors from immunocompetent cells (Ganguly and Das, 1994). Treatment of human leukemic cells with mononuclear cell-conditioned medium prepared from rice extracts (but not rice extracts) resulted in a marked inhibition of growth and increase in mature monocytic functions. This suggests that there may be mediators produced by peripheral blood mononuclear cellcapable of triggering leukemic cells to differentiate into mature, functioning cells. Therefore, we suggest that the anti-tumor activity induced by rice is due to stimulation of an immunomodulating response rather than direct inhibition of growth of leukemic leukemic cells. The results showed that black rice extracts are safe for cultured peripheral blood mononuclear cell because there was no cytotoxicity observed even at higher concentrations up to 10 mg/mL.

However, the immunopotentiating effect of rice is moderate, and not as great as medicinal herbs (Wang et al., 1997; Fisher and Yang, 2002), thus rice may not have a major therapeutic role in leukemia treatment. This moderate immunomodulating effect against leukemic cells, without cytotoxicity to normal MNC, suggests that rice might be suitable for clinical application as an adjuvant treatment in leukemic patients. Since rice is generally accepted as a staple food, black rice extract could be both good energy sources and biological response modifiers in leukemic patients.

Black Rice extract and related derivatives have been reported as being capable of modulating immune functions. Modified arabinoxylan rice bran can augment the secretion of TNF-a and IFN-c from human peripheral blood lymphocytes (Ghoneum and Jewett, 2000) and can enhance the phagocytic activity of macrophages (Ghoneum and Matsuura, 2004).

Over-view of Glutathione

Glutathione is probably the most important antioxidant present in cells. Therefore, enzymes that help generate Glutathione are critical to the body’s ability to protect itself against oxidative stress. Alcohol has been shown to deplete GSH levels, particularly in the mitochondria, which normally are characterized by high levels of Glutathione needed to eliminate the reactive oxygen species (reactive oxygen species ) generated during activity of the respiratory chain. Mitochondria cannot synthesize Glutathione but import it from the cytosol using a carrier protein embedded in the membrane surrounding the mitochondria. Alcohol appears to interfere with the function of this carrier protein, thereby leading to the depletion of mitochondrial Glutathione (Fernandez–Checa et al. 1997).

Oral Glutathione Increase Tissue Glutathion Levels

Tak Yee Aw et al. in 1991 demonstrated that oral glutathione increases tissue glutathione in animal.
“Mice were given an oral dose of glutathione (GSH)(100mg/kg) and concentrations of glutathione were measured at 30,45 and 60 min in blood plasma and after 1 h in liver, Kidney, heart, lung, brain, small intestine and skin. In control mice GSH concergtratin in plasma increased in 30 UM TO 75 UM within 30 min of oral glutathione administration, consistent with a rapid flux of glutathione from the intestinal lumen to plasma. Under these GLUTATHIONE-SUFFICIENT CONDITIONS, NO INCREASED OVER CONTROL VALUES WERE OBTAINED IN gsh concerntration in most tissues except lung over the same time course. Administration of the equivalent amount of the constituest amino acids glutamate, cysteine, and glycine, resulted in little change in glutathione concentrations in all tissues in glutathione-deficient animals. Thus the results show that oral glutathione CAN INCREASE GLUTATHIONE concentrations in several tissues following glutathione depletion, such as can occur in toxicological and pathological condition in which glutathione homeostasis is compromised.

Lung Disease Cause

Many lung diseases are associated with low glutathione levels, including cystic fibrosis, chronic obstructive pulmonary disease and acute respiratory distress syndrome. This study confirms that an oral dose of glutathione can increase blood, tissue and extracellular glutathione levels and that the absorption of glutathione was dependent on the cystic fibrosis transmembrane conductance regulator. It is also known that the levels of glutathione in the epithelial lining fluid are diminished in a number of lung disorders and environmental exposures including ARDS,9 idiopathic lung fibrosis, lung transplantation, HIV infection, alcohol abuse, asbestos, and cystic fibrosis. Studies in cystic fibrosis have partially illuminated mechanisms the lung uses to place glutathione into the epithelial lining fluid.

150mg/per lb is need

The pharmacokinetic profile of an oral bolus dose of Glutathione (300 mg/kg) was determined in mice. Plasma, ELF, bronchoalveolar lavage (BAL) cells and lung tissue were analyzed for Glutathione content. There was a rapid elevation in the Glutathione levels that peaked at 30 minutes in the plasma and 60 minutes in the lung, ELF and BAL cells after oral Glutathione dosing. Oral Glutathione treatment produced a selective increase in the reduced and active form of GSH in all lung compartments examined. Oral Glutathione treatment (300mg/kg) resulted in a smaller increase of Glutathione levels. To evaluate the role of CFTR in this process, Cftr KO mice and gut corrected Cftr KO-Tg mice were given an oral bolus dose of GSH (300 mg/kg) and compared to wild type mice for changes in GSH levels in plasma, lung, ELF and BAL cells. There was a 2-fold increase in plasma, a 2-fold increase in lung, a 5-fold increase in ELF, and a 3-fold increase in BAL cell GSH levels at 60 minutes in wild type mice, however Glutathione levels only increased by 40% in the plasma, 60% in the lung, 50% in the ELF*, and 2-fold in the bronchoalveolar lavage cells within the gut corrected Cftr KO-Tg mice.

* ELF gen, a new isoform of beta-G-spectrin in the developing brain cells. Based on its expression pattern, ELF may have a role in neural stem cell development and is a marker of axonal sprouting in mid stages of embryonic development. Oncogene (2002) 21, 5255 ± 5267. doi:10.1038/sj.onc. 1205548, ELF gene expression

Liver in Detoxification

Glutathione is a vital substance in detoxification and cell. Glutathione plays a key role in the liver in detoxification reactions and in regulating the sulphur compound compounds (thiol-disulfide status) of the cell. Under conditions of oxidative stress, the liver exports oxidized glutathione into bile in a concentrative fashion, whereas under basal conditions, mainly reduced glutathione is exported into bile and blood. physiology.

Glutathione regulation in liver is based on a homeostatic feedback inhibition mechanism. The availability of cysteine is a critical factor in the regulation of synthesis. Turnover in liver is determined mainly by the efflux of glutathione into both sinusoidal blood and bile and its subsequent degradation. The constituents of exported glutathione are conserved by hydrolysis and cellular uptake mainly in the kidney and intestine as governed by brush-border -y-glutamyltranspeptidase. Thus, one can view the liver as a glutathione-generating factor which supplies the kidney and intestines with the constituents for glutathione resynthesis.

Glutathione Levels Linked to Cell Survival

Ability of oral Glutathione to serve as a precursor for hepatic GSH. Comparison with other precursors
Intracellular Glutathione protects the cells against several agents that are potentially harmful, such as hydroperoxides (Chance et al. 1979), xenobiotics (Orrenius & MoldCus, 1984) or ionizing radiations (RCvesz & Edgren, 1982). In many cases, cellular Glutathione levels are lowered and to restore these levels may be very important for cell survival. This is the case in fasting which decreases the hepatic levels of Glutathione. Fasted animals are more susceptible to hepatic damage by drug overdosage than fed animals. A major reason for this susceptibility is the fall in GSH levels. Here we show that administration of oral GSH increases the hepatic levels of GSH in fasted rats.

Excessive L-cysteine Gives Rrise to Free Radicals Damage

In liver, L-cysteine availability is the limiting factor for Glutathione synthesis (Tateishi et al. 1974); therefore, the supply of this amino acid is essential to restore the physiological levels of Glutathione. However, administration of free L-cysteine is dangerous because of its toxicity. The toxicity of this amino acid has been demonstrated in several types of cells and organs such as brain (Olney et al. 1972; Viiia et al. 1983a) and liver (Viiia et ul. 1980). In isolated hepatocytes, we observed that incubation with L-cysteine promotes a decrease in Glutathione levels (Viiia et ul. 1978) and several other signs of cytotoxicity. These side effects are due to very rapid auto-oxidation (Viiia et al. 1983b) which gives rise to free radicals (Saez et al. 1982). The toxic effects of L-cysteine do not occur when the oxidation rate of the amino acid is maintained very low (Beatty & Reed, 1980); therefore, it is important that L-cysteine reaches the liver slowly as is the case after the administration of oral Glutathione. All these factors explain why the cell accumulates free thiols as Glutathione, which acts as a reservoir of L-cysteine (Tateishi et al. 1977).

Glutathione is not an essential nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine.

What is R-Alpha Lipoic Acid

According to the American Cancer Society in 1937 researchers first identified R alpha lipoic acid (know here after as lipoic acid) isolated from bacteria, this compound that was investigated then, in 1939 other research demonstrated the antioxidant activity of lipoic acid. 

Dr. Bilska et al. 2005, stated that naturally occurring alpha lipoic acid was isolated from bovine liver in 1950. When one is looking of natural Lipoic acid one needs to keep in mind that only the  R- isomer is naturally synthesized by animals or plants organisiums and is easily bound to protein. R alpha lipoic acid was first believed to be part of vitamin B complex.  Present the majority of research demonstrates that lipoic acid is not a vitamin. It is synthesized in human and animal body in mitochondria (The engine of the cells.), where, similarly as in bacterial and plant cells, octanoic acid and cysteine, which is the source of sulfur, are direct precursors of lipoic acid.

Alpha Lipoic Acid improves Liver Function

Alpha lipoic acid was shown to be hepatoprotective to improve liver circulation, and treat chronic liver
diseases, including  jaundice, hepatitis, cirrhosis,and hepatic coma, to treat diabetes, and diabetic neuropathy to alter carbohydrate metabolism, histidine metabolic disorders, blood pyruvate and lactate levels, to treat psychiatric diseases, Botkin’s disease, antimony poisoning, mercury poisoning, atherosclerosis, coronary atherosclerosis, cerebrovascular diseases, ethionine-damaged liver,  potassium cyanide poisoning, streptomycin intoxication, mushroom poisoning, lower cholesterol, reverse barbiturate anesthesia, experimentally reduce voluntary alcohol intake, and augment potassium tolerance .

Diabeties and Alpha Lipoic Acid

One of the most studied clinical uses of alpha lipoic acid is the treatment of diabetes and diabetic neuropathy alpha lipoic acid has also been used experimentally and/or clinically to prevent organ dysfunction, reduce endothelial dysfunction and improve albuminuria, treat or prevent cardiovascular disease, accelerate chronic wound healing, reduce levels of ADMA in diabetic end-stage renal disease patients on hemodialysis, burning mouth syndrome, reduce iron overload, treat metabolic syndrome, improve or prevent age-related cognitive dysfunction,  prevent or slow the progression of Alzheimer’s Disease, prevent erectile dysfunction (animal models but anecdotally applies to humans as well), prevent migraines, treat multiple sclerosis  treat chronic diseases associated with oxidative stress reduce inflammation, inhibit advanced glycation end products (AGE), treat peripheral artery disease.

Free Radicals Linked to Heart Disease

One of the causes of heart disease is free radical damage this process has been implicated as a factor in the aging process of the heart and other organs inducing diseases. 

According to the Center for Disease Control and Prevention CDC Heart disease has been the leading cause of death in the United States for the past 80 years and is a major cause of disability.  A new approach to treating heart disease is needed, unless we change directions this statistic will not change. Heart aging is accompanied by changes that are progressive, pervasive, injurious to one’s health, and, as far as allopathic medicine is concerned is, irreversible.

Cardiovascular diseases such as hypertension, atherosclerosis, and congestive heart failure are at epidemic proportions in the elderly population, and are the leading cause of morbidity and mortality among this group.

Cardiovascular autonomic neuropathy is characterized by reduced heart rate variability, and is associated with increased risk of mortality in diabetic patients. In a randomized controlled trial of 72 patients with type 2 diabetes mellitus and reduced heart rate variability, oral supplementation with 800 mg/day of lipoic acid for 4 months resulted in significant improvement in 2 out of 4 measures of heart rate variability compared to placebo, Dr. Ziegler D et al. 1997.

Lipoic Acid Restored Myocardial Vitamin C Levels and
Reduced Free Radical DNA Damage

In vivo study determine the extent of age-related myocardial free radical damage, Free radical production, antioxidant status, and free radical DNA damage were measured in hearts of young and old male Fischer rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of free radicals production compared to young rats. To investigate whether dietary supplementation with (R)-a-lipoic acid was effective at reducing free radical damage, young and old rats were fed a standard chow diet with or without 0.2% lipoic acid based on weight feed for 2 wk before the animals were tested. Cardiac myocytes from old, Lipoic acid supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from un-supplemented, young rats. Lipoic acid supplementation also restored myocardial vitamin C levels and reduced free radical DNA damage. The study indicates that the aging heart is under increased mitochondrial-induced free radical damage, which is significantly mitigated by lipoic acid supplementation.  2001 JUNG H. SUH et al., Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-a-lipoic acid. FASEB J. 15, 700–706 (2001)

Oral adminstration of Alpha Lipoic Acid Restrored Age Associated Decline

The causes for this age-related decline in myocardial mitochondrial function are not completely understood. It has been shown that the proportion of the active form of pyruvate oxidoreductase (enzyme that catalyzes the COENZYME A-dependent oxidative decarboxylation of pyruvate to acetyl-coenzyme A and carbon dioxide e.g. cleaves the free radical/oxidative stress inducer into two harmless substances.). Feeding old rats Lipoic acid reversed the age-associated decline in Lipoic acid -dependent oxidoreductase activity.

This may also explain why we only observed a beneficial effect of Lipoic acid only in old and not in young animals. Other necessary cofactors necessary for mitochondrial function, such as carnitine and cardiolipin, also decline with age. Carnitine loss, for example, can limit the transport of fatty acids into mitochondria, which is the major source for Adenosine-5'-triphosphate (ATP) synthesis. In addition, decline in cardiolipin (Important component of the inner mitochondrial membrane) has been shown to decrease substrate transport in isolated mitochondrial preparations and lower cytochrome c oxidase activity (It is the last enzyme in the respiratory electron transport chain of mitochondria located in the mitochondrial membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it binds four protons from the inner aqueous phase to make water, and in addition translocates four protons across the membrane, helping to establish a transmembrane difference of proton electrochemical potential that the ATP synthase then uses to synthesize ATP.).

Present findings suggest that (R)-a-lipoic acid supplementation is a safe and effective means of improving systemic decline in over all metabolic function and also increase protection against both endogenous and external production of free radical damage.

One possible physiological consequence of these decreased cofactors would be loss of ATP production, which may lead to cardiac stiffness. To maintain myocardial function, a constant supply of ATP is required and small reserves are maintained. This suggests that when energy supply is interrupted (ischemia) or impaired (aging), ATP levels decline rapidly. Like systolic contraction, diastolic relaxation also requires high levels of ATP, because ATP acts as an allosteric effector (A small molecule that reacts either with a nonbinding site of an enzyme molecule, or with a protein molecule, and causes a change in the function of the molecule. Also known as allosteric modulator.)  to disassociate actin from myosin (comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes).

Thus, any decrement in mitochondrial ATP synthesis affects cardiac stiffness appreciably. A decline in ATP synthesis also compromises calcium reuptake into the sarcoplasmic reticulum from the cytosol (The liquid component of the cytoplasm surrounding the organelles and other insoluble cytoplasmic structures in an intact cell where a wide variety of cell processes take place.), again affecting myocardial relaxation. The sodium/calcium transporter is also energy dependent, and a decline in myocardial ATP levels would thus slow cardiac relaxation by decreasing the rate of calcium removal from the cytosol (fluid around the cell). It is notable that a general attribute of myocardial aging is a prolonged cytosolic calcium transient and slower myocardial relaxation rate.

The exact physiological consequences associated with these cellular changes remains to be completely clear.
Although these changes may not affect the heart’s function under normal conditions, it is possible that a loss in bioenergetic capacity along with antioxidant protection may severely limit the hearts ability to respond to physical stress.

Diabetes

According to American Diabetic Association in 2007, diabetes was listed as the underlying cause on 71,382 death certificates and was listed as a contributing factor on an additional 160,022 death certificates. This means that diabetes contributed to a total of 231,404 deaths.

Lipoic acid presents beneficial effects in the management of symptomatic diabetic neuropathy and has been used in this context in Germany for more than 30 years. Lipoic acid has been shown to possess a number of beneficial effects both in the prevention and treatment of diabetes in experimental conditions.

Superoxide Dismutase

In mammals there are several types of superoxide dismutases, which differ with respect to their location in the cells and the metal ions they require for their function. For example, a copper–zinc superoxide dismutas is present in the fluid filling the cell (i.e., the cytosol) and in the space between the two membranes surrounding the mitochondria.

Superoxide dismutase is a scavenger of superoxide radicals and is present in all oxygenmetabolizing cells. In human and other mammals superoxide dismutase is a copper (Cu2+)- and zink (Zn*+)-containing enzyme. Loss of Cu2+ causes loss of enzyme activity, whereas Zn does not appear to be part of the active site.

The enzymes superoxide dismutas and catalase have been reported to have a radioprotective effect if added to cultured lymphocytes immediately after irradiation (NORDENSOetN al. 1976). The frequency of chromosomal aberrations was significantly decreased by the enzymes, both combined and alone.  Hereditas 89: 163-167 (1978)

Furthermore, a manganese–containing superoxide dismutas is present in the mitochondrial interior (i.e., matrix). Both of these enzymes are critical for prevention of Reactive oxygen species –induced toxicity (Fridovich 1997).  Another type of superoxide dismutas is found outside the cells. The effects of chronic alcohol exposure on the cellular content or activity of superoxide dismutases are controversial, with reports of increases, no changes, or decreases, depending on the model, diet, amount, and time of alcohol feeding.

Radioprotective Effect on Human Chromosomes by Superoxide Dismutas

In 1973 La Avelle et al. showed that superoxide dismutas has been found to protected simple organisms from the effects of radiation damage.   Then in 1975 Petkauk et al and confirmed by Elly et al in 1976 demonstrated that bone marrow stem cells of mice from radiation damage. A radioprotective effect of catalase has also been reported.

As free radicals are known to be involved in the mechanism of lipid peroxidase lation of cellular membranes and also to be deleterious to DNA, the observed synergistic action of the enzymes might be due to interference at different steps of oxidative reactions, in which harmful radicals e.g. hydrozyl radicals are produced. Addition of the enzymes before irradiation had about the same effect as addition afterwards, suggesting that the clastogenic affect continues for some time after the irradiation.

The primary radicals produced by radiolysis of water show a rapid decay, sometimes associated with the generation of secondary radicals. The present observations indicate that chromosome breakage is caused not only by primary but also by secondary radicals generated in the culture medium, and that the enzymes may act preferentially by interfering with the production of secondary radicals. These findings are in accord with the report by Petkauch Elacek et al, (1976) on a protective effect in irradiated mice by superoxide dismutases (reduced lethality) even when the enzyme was administered 1 h after irradiation.

Catalase

Enzymes involved in the elimination of reactive oxygen species (reactive oxygen species) include catalase, superoxide dismutases (SODs), and glutathione peroxidase.

Catalase is a tetramer of four polypeptide chains, each over 500 amino acids long. It contains four porphyrin heme (iron) groups that allow the enzyme to react with the hydrogen peroxide. Catalase is a common enzyme found in nearly all living organisms that are exposed to oxygen, where it functions to catalyze the decomposition of hydrogen peroxide to water and oxygen. Catalase has one of the highest turnover numbers of all enzymes; one catalase enzyme can convert 40 million molecules of hydrogen peroxide to water and oxygen each second. The optimum pH for human catalase is approximately and has a fairly broad maximum (the rate of reaction does not change appreciably at pHs between 6.8 and 7.5).

Catalase serves to detoxify hydrogen peroxide and various other molecules. One way that catalase eliminates hydrogen peroxide is by catalyzing a reaction between two hydrogen peroxide molecules, resulting in the formation of water and oxygen O ₂.

Hydrogen Peroxide into Water

In addition, catalase can promote the interaction of hydrogen peroxide with compounds that can serve as hydrogen donors so that the hydrogen peroxide can be converted to one molecule of water, and the reduced donor becomes oxidized (a process sometimes called the peroxidatic activity of catalase). Compounds that can provide these hydrogen atoms include beverage alcohol (i.e., ethanol) and methanol.

Free Radicals induce over 200 Diseases

Oxidative stress is now recognized to be associated with more than 200 diseases, as well as with the normal aging process. In nearly all cases it is not clear whether the role is a causative one or whether the oxidative damage is simply a sequela of other types of tissue injury. Some of the effects of ionising radiations are associated with formation of free radicals and possibly of peroxides species. Such effects are often reduced under anaerobic conditions (absence of oxygen) and increased in the presence of oxygeni.

Stoping The Damage To Tissue

There is increasing evidence that oxygen free radicals are associated with the process of ischemia-reperfusion injury not only in regard to myocardial infarcts but also with periods of ischemia involving the brain (cerebral vasospasm), kidney, intestine, and other organs. The bulk of the evidence stems
from the ability of antioxidants to offer a degree of protection against the injury, a correlation between oxidative damage (e.g. lipid peroxidation) and tissue necrosis, and more recently direct and indirect measurement of oxygen free radicals during the reperfusion phase. Furthermore a number of drugs commonly in use, especially for the treatment of a variety of symptoms of coronary heart disease, have been shown to have strong antioxidant properties, Guo Dong Ma et al 1992.

Many of the known catalase inhibitors including sodium azide and cyanide are also respiratory poisons. When such substances are administered to animals in large doses, they reduce the sensitivity of animals to X-rays (Bacq, 1950).

Catalase is, however, much more sensitive than respiration to poisoning by sodium azide, and it should be possible to obtain considerable inhibition of catalase without reducing the respiration. Under such conditions it might be possible to obtain increased radiosensitivity.
An effect of increased sensitivity in tumours, as compared with other tissues, might be obtained by inhibition of catalase because the catalase content of tumours is extremely low, being about one-hundredth of that of liver tissue.

Although the amount of catalase present in tumours seems very great when measured at the usual (M/200) concentration of H₂0₂, the activity at naturally occurring concentrations of hydrogen peroxide may be of the same order as the respiration of the tissue, because catalase activity is proportional to the concentration of peroxide.

Catalase decomposes hydrogen peroxide (H₂0~) at an extremely high rate. Hydrogen peroxide is in itself cytotoxic, but can also by reacting with superoxide radicals produce highly deleterious hydroxyl radicals. In red blood cells catalase protects against oxidizing agents. Catalase probably protects red blood cells from the deleterious effects of oxidizing agents ( Aebaind Sube et al 1971).

The effect of both enzymes catalase and superoxide dismutases together was larger than the effect of each enzyme alone. The increased protective effect of both enzymes together was. An increased protective effect of both enzymes together also has been found in previous studies (Nordensot et al 1976; and 1977 ). Demonstrating the synergistic effect of SOD and catalase in protecting red blood cells against peroxidative hemolysis.