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Uses of Ozone Therapy in the Treatment of Cancer and Other Pathologies

…. In November of 1902, The Lancet published an article by Dr. George Stoker, a physician at the London Throat Hospital in which he described the benefits of treating tinnitus and chronic mid-ear deafness with ozone. Fourteen years later, on October 21 1916, The Lancet published another article by Stocker entitled “Ozone’s Surgical Applications”. In this article, Dr. Stoker described ozone’s efficacy to treat war wounds in tests performed with 21 patients at the Queen Alexander Military Hospital. In the article’s conclusions, Dr. Stoker noted: “Ozone greatly stimulates the flow of blood to the wounded area, its germicide effect destroys all the hostile microorganisms and it shows a great potential in aiding the formation of oxihemoglobin”. The articles goes on to state that ozone treatments represent a great benefit not only at the medical level but at the scientific, humanitarian and economic levels. A year later, Stoker presented another article with the same title where he discussed 78 more cases in which he demonstrated again the efficacy of ozone treatments.

(…) The therapeutic usage of ozone, administered via a mix of oxygen (O2) and ozone (O3), destroys a multitude of bacteria, viruses and fungus, augments the transport of oxygen to affected areas or organs and stimulates the enzymatic anti-oxidant systems, balances the immune system and has a potent anti-inflammatory and analgesic effect. To date, no secondary effects have been found during ozone treatments and, for this reason, its benefits should be put to use for patients that suffer oxidative, degenerative, ischemic, immune or tumor processes. Its efficacy has been proven as a complementary therapy in cancer patients. Dr. Pérez Olmedo, Founder of the first Intraperitoneal Ozone Therapy Unit in Spain, gave a presentation about the usefulness of ozone in cancer treatments at the 3rd International Congress on Complementary and Alternative Cancer Treatments that took place on October 31-November 1st 2009 in Madrid, sponsored by the World Association for Cancer Research (WACR) and by this magazine.

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.-Dr. Pérez Olmedo, are you a conventional doctor? What are your qualifications?

I am a family doctor and I am also an orthopedic technician and a registered nurse. I practice conventional medicine, not alternative medicine. Unfortunately, ozone therapies are often practiced by individuals who are not doctors. In other countries, more advanced in their use of medicine, many physicians use ozone on a regular basis.

 

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-What type of ozone research do you do?

At the moment I am focused on researching the usefulness of intraperitoneal ozone therapy in cancer patients and odontology. I also study the applications of ozonated oil in the development of skin care products. I carry out this research with a pharmacist, Mr. Manuel Carrascal. We use our proprietary blend of ozonated oils to manufacture creams, balms and toothpaste… we are very excited because these products maintain some of the regenerative properties of ozone and have proven to be effective in tumor-related radio dermatitis or herpes zoster.

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.-How do you come to know about the benefits of ozone in different pathologies?

By pure necessity and by chance, I suffered from back pain for years and, being a doctor, I did a lot of research about treatments for back pain. After trying a few options, a neurosurgeon told me that the only solution for my vertebrae was to operate. I told him about ozone and that Dr. Verga, in Italy, was performing very successful para-vertebral treatments with ozone without secondary effects. He insisted that it wouldn’t work in my case but I decided to explore ozone treatment and did not do an operation, I tried the ozone treatments instead. The incredible thing was that, after years of living in pain, it went away after only one session! I thought that was such an extraordinary occurrence that it forced me to change radically my way of understanding, practicing and studying medicine. I think any doctor who knows a therapy that can help a patient has de duty of using it or recommending it, especially if he/she considers the therapy to be better and with less secondary effects that those conventionally used. It is sad that some of these therapies, particularly ozone, are not included in our public health systems. Dr. Eusebio Sala Planell, a vascular surgeon and pioneer of ozone therapies in Spain, often tells the story of an 80 year old woman who was already on the operating table, ready to have one of her legs amputated. At that moment, she decided to not get the operation and try ozone treatments (auto-hemotherapy and ozone bags). The patient had become acquainted with the possibility of ozone treatments a few days prior to the operation date. The 80 year old lady was able to save her leg and lived ten more years. At our clinic, OZONOTHERAPY&HEALTH we have had the chance to treat different cases but with equal success. In fact, as time goes by, we cannot but be surprised at the great help that ozone can bring to numerous pathologies.

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-      .- Why do you think that ozone therapies are not discussed in medical schools or in continuing education courses for certified MDs?

 

I don’t know the answer to that question but I think it is probably because the vast majority of these courses are organized or financed by the pharmaceutical industry and it has no interest in seeing the benefits of ozone publicized. Nobody told me in medical school about the benefits of ozone. And my professors didn’t know about it either. This is still true in most medical schools. Because of this, most doctors finish their medical degrees thinking that ozone therapies are a secondary resource. This is a big mistake but fortunately the situation is not the same everywhere. In Germany, more than 15,000 MDs prescribe ozone treatments regularly. In Cuba, all hospitals, even pediatric hospitals, have ozone therapy units. In Turkey or Mexico, the medical practice of ozone therapy is growing tremendously. The successful results of these therapies will end up standing up for themselves.

 

-          .-The use of ozone as a medicine is authorized in Europe….

 

True. In fact, ozone is considered to be a drug by the European Medicines Agency. The truth is that ozone can be used as a therapeutic tool that works and has no side effects. Every doctor should be counting on it for his/her prescriptions. Because of its potent germicide and oxygenating action it is a perfect therapy for the treatment of wounds, burns or ulcers… and also for many other pathologies. The more I read, study and think about it the more I wonder how is it possible that not more doctors have taken an interest in ozone therapies. And the answer that comes to my mind when I ponder this question is that medical care has become first and foremost a big business and that curing people is of secondary interest. Nobel Prize winner Richard Roberts (1993) said “the drug that cures completely is not profitable”; it is more profitable to give patients drugs that alleviate but not cure for life. In the case of ozone, the issue is that it cannot be patented or bottled, where is the business there?

 

-        .-  In what pathologies does ozone provide an unquestionable benefit?

 

Ozone has an ample spectrum of applications. It is the strongest oxidizer after fluoride and radical hydroxyl. This property allows the body to generate other compounds able to stimulate a selective and potent antioxidant enzymatic response. In my opinion, ozone should be an obligatory therapy in any pathology in which there is oxidation: cardiovascular disease, degenerative disease, neurological diseases, arthritis… Diabetes is a great example of continuous and permanent oxidation as all the complications brought about by diabetes are due to oxidation. Diabetes is an illness that works as a manufacturing plant of free radicals 24/7. The antioxidant defenses of diabetics cannot keep so many free radicals at bay and other illnesses, secondary to diabetes, end up afflicting the patients. For this reason, diabetic patients have the highest rates of amputations, heart attacks, ictus, kidney failures, blindness and cancer. We know that it is critical to control rigorously blood sugar levels in diabetic patients and the diabetes treatment focuses on this aspect but we should also be taking measures to ensure that patients maintain a high level of antioxidant defenses. In this sense, ozone therapy is the perfect complement.

 

-       .-   If ozone is oxidizing, how can you explain that it improves the body’s defenses?

 

Ozone’s behavior is a paradox. It is indeed a potent oxidizing agent outside the body, for instance, in water, it is capable of killing any pathogenic microorganism 3,000 times faster than chlorine, but on the inside of the body it causes a series of reactions that creates antioxidant molecules, how? Ozone has a special affinity for any molecule that has a carbon double bond. This structure is very frequent in phospholipids and hence in all cell membranes. When ozone makes contact with this carbon double bond structures, for instance, in the blood, it reacts in nanoseconds causing the formation of aldehydes, peroxides, hydrogen peroxides and ozonides. These compounds bring about ozone’s therapeutic effects as they act as a signal molecule and activate different systems, amongst them the enzymatic antioxidant made out of three main enzymes: superoxide dismutase, catalase and the glutathione peroxidase system. These systems regulate the oxidative stress that takes place in our bodies every day. In addition, ozone activates the oxygenation of the tissues. Finally, it is anti-inflammatory, analgesic and balances the immune system.

 

-          .-What role can ozone therapies play in cancer treatment?

 

Just like the diabetic patient, cancer patients are also a manufacturing plant of free radicals. If we treat cancer patients conventionally, chemotherapies and radiotherapy are also highly oxidizing. Unfortunately, these patients’ normal cells suffer the oxidizing attacks of chemotherapy and radiotherapy, which can end up causing other types of cancer. It is clear that a chemotherapy agent can kill a cancer cell, but in order to kill all of them the doses have to be so high that most patients cannot stand the treatments, particularly when their cancer is already advanced. Conventional cancer therapies attack the bone marrow, which is where our defense cells are manufactured. This is the reason why patients are asked to “rest” between chemotherapy sessions, so that their bodies are given a chance to recover. If they overcome the first treatment and their defenses go up, they are given another oxidizing attack. This would be acceptable if our bodies could resist these attacks for a long time, but the truth is that in most cases the reality is different and the resting times allow the cancerous cells to become resistant to the treatment, which forces doctors to try new types of chemotherapy or to give more chemotherapy cycles. What is the reality of the treatment then? Cancer progresses and metastasis take place. Except in some cases, like some types of leukemia, some pediatric cancers, lymphomas, testicular cancer and a few others, the illness continues to progress. In the cases where the illness continues, patients are treated empirically, trying new and different treatments just in case it works.

 

 

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 Dr. Julio Devesa, Dr. J. Antonio Marques, Dr. Juan José Gude and Dr. Pérez Olmedo       

 

 

 

 

 

 

 

 

 

 

 

Uses of Ozonetherapy  in  the treatment of Cancer and other Pathologies

 

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.-When should ozone therapies be applied in cancer patients?

In my opinion, every cancer patient should receive at least one cycle of intra- peritoneal ozone therapy from the day of diagnosis. Ozone, in addition to being a potent germicide, increases the oxygenation of tissues, acts on the inflammatory-anti-inflammatory cascade regulating it, generates cytokines such as interferon gamma, the TNF (tumor necrosis factor) alpha and other “good” eicosanoids such as prostacyclin. All these compounds exhibit anti-tumor capabilities and are manufactured by the body instead of synthetically thanks to the ozone therapy. Ozone also activates enzymatic antioxidant systems (superoxide dismutase, catalase and the glutathione peroxidase system). The extra generation of prostacyclin as a result of intra peritoneal ozone therapies is possibly the key to the therapy’s anti-tumor effect.

In addition, an environment rich in ozone inhibits the growth of cancer cells. We blow intra peritoneal ozone in great quantities so that the tumor area experiences an increase in oxygen for several days. In addition, this inhibits neovascularization or neoangiogenesis, which stimulates the tumor area or causes lack of oxygen.

- Why are patients with advanced cancer the main oncology testing ground?

Terminal or “incurable” patients with advanced cancer processes are often offered experimental treatments or treatment combinations. The problem is that unfortunately they are also the ones who suffer the side effects of these sometimes unproven treatments. As of today, oncology researchers have not found one drug that attacks cancer cells without affecting the healthy ones. Most of these terminal patients think that the treatments they are being offered as a last resort might cure them, and doctors think the same, but the reality is different. While experimentation with humans is necessary, the drugs usually have great side effects that in many occasions precipitate the patient’s death faster than the illness itself.

In this sense, I always remember my father’s dramatic death. He suffered from Sezary Syndrome, a T cell skin cancer. He died in two months. His leucocytes fell down to zero and he could not overcome the treatment at any point. Without treatment he would have lived a lot longer but we accepted a new product that, according to the laboratory, allowed patients with this illness to live longer than those patients who did not have the treatment. The reality is that when you read the studies that support the sales permits for new and costly anti-tumor drugs you can see that the group of patients that tried the drug had an increased “life expectancy” of days or weeks, at most a couple of months. This is the case Sorafenib for advanced liver cancer or Riluzol for for lateral amyotrophic sclerosis, and the worst thing is that they don’t increase patients’ quality of life! On the contrary, chemotherapy agents offer a little longer life span at a high cost in terms of life quality. This is the case with all the products that are used to treat advanced, incurable cancer.

--What are the results experienced by cancer patients who choose intraperitoneal ozone therapy?

We have treated more than 80 patients and we have performed more than 350 intra peritoneal ozone sessions. We have many data points that allow us to say that these patients experience unquestionable positive responses to the treatments, which can be measured both clinically and analytically. Ozone intraperitoneal therapies affect positively the patients’ quality of life, increase their life span and slow down the progression of metastasis. In addition, patients treated with intraperitoneal ozone respond better to chemotherapy and radiotherapy treatments. We have treated many types of cancer and ozone intra peritoneal therapy has always worked. Clearly, we would need to treat at least 50 patients with each cancer type in order to accelerate our research and lend it more weight. At any rate, there are publications about the effect of intra peritoneal ozone in cancer patients, such as the one published by Dr. Schulz, from the University of Marburg (Germany) in the Journal of Cancer.

-How do you apply intraperitoneal ozone?

We anaesthetize the patient and then introduce the ozone through a catheter. Initially there are at times side effects from the anesthesia and the procedure but at the end of the treatment the patient’s body improves. And when you apply ozone in an area where there is a tumor an adverse environment for the progression of the metastasis and the tumor growth is created. Patients show a clinical improvement and his/her life quality and expectancy improve. It also helps with the side effects of chemotherapy. In the same way, it helps when our patients are receiving radiotherapy because ozone improves the tissues’ oxygenation.

 

Introduce the ozone through a catheter

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Medical Team:Dr. Marques, Dr. Pérez Olmedo. Dr. Devesa Regueiro and the Nurse María José Seoane  

 

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                 .- If  if this is the case, why don’t more oncologist use ozone as a complementary treatment?

I think it is because sometimes oncologists exclude all treatments other than the one they administer. Even patients end up thinking that their illness can only be treated by an oncologist. The most surprising fact is that some oncologists reject the visible improvements in some of their patients when they try other treatments. In some instances, oncologists are not interested in exploring whether other treatments have actually contributed to their patient’s improvement.

- what are the most important steps that your intra peritoneal ozone practice has experienced in the four years since we last interviewed you?

The most important step has been the consolidation of our medical team. Dr. Marques Magallanes de Regojo, has been an important addition to the five doctor team. He is an internist who today shares with us the conviction that ozone is an essential tool in treating different pathologies, especially in cancer patients. Four years ago we had treated 14 patients, now we have treated more than 50 and we have performed more than 350 sessions. This experience has allowed us to collect a great amount of information that will help us improve our treatment protocols and results. Some of this information will be published and our experiences described so that hopefully they will awaken the interest of those who dedicate their lives to treat and cure cancer. We know already how the liver, kidney, marrow and other organs respond to large doses of intraperitoneal ozone. We would be glad to share our information with other doctors who might be interested in the topic.

At the same time, we have also treated dogs afflicted with cancer with intraperitoneal ozone. Thanks to Mary-Lis Urueña, her Great Dane with bone cancer received several treatments and lived for seven months enjoying a great quality of life and no side effects. During the last intraperitoneal treatment, she was anesthetized with electro acupuncture because she had previously become temporarily blind as a reaction to anesthesia. The results with the electro acupuncture were fantastic.

- Where any of the patients you treated particularly successful?

Most of our patients use ozone as a complementary treatment, for most of them, the ozone is applied rectally or intravenously, few of them actually choose intraperitoneal ozone treatments, but all of them respond well to ozone. Clearly, the intraperitoneal application is much more effective than the other techniques in terms of treating symptoms as well as when measuring their biochemical parameters.

I especially remember David, a 33 year old man who came with his mother Susana, an admirable woman who fought for him like I have never seen. David had a melanoma with metastasis in the brain, peritoneum, bladder, pancreas and liver. At the point where they came to see me, he spent his life on a couch, waiting to die. We treated him with intraperitoneal ozone and soon after the treatment he was fishing, shopping, and leading quite a normal life. He went from waiting to die on a couch to living life. His condition improved clearly, some metastasis disappeared and others were reduced. We waited a few months and his mother brought him again from Seville to be treated a second time, with the same positive results. His mother was also trying other treatments and a few months after she called us to perform a third treatment but he was at the hospital by then and he passed away soon after. I wish David could have received the treatments today because we know a lot more now, but it is clear that he and his mother helped us get to where we are today. Each of our patients comes with a very different situation and each of them has benefited from ozone

- Given these results, how can you explain the indifference of oncologist?

For us it is incomprehensible. Multinational pharmaceutical companies have invested billions of euros in essays and research searching for anti-tumor drugs that increase the patients’ life span and, as it turns out, they are looking for something that already exists! And the most amazing fact is that they don’t want to research and perform “serious” essays with ozone. Why? Because it cannot be patented. Hence, they have chosen to send the message that there are no studies that demonstrate ozone’s efficacy… not saying that if there is not more research carried out is because they don’t want to invest the money.

The saddest part of all this is that the (Health) Administration doesn’t want to study what has been achieved with ozone up to now. They prefer to continue looking elsewhere and spending billions of euros in iatrogenic products and only increase the patients’ life span a few weeks at best. Perhaps this is one of the reasons why many high ranking officials from our health Administration end up holding very lucrative jobs in these multinationals. Of course, executives from the same multinationals populate the Administration’s top management. The same is true for the “opinion leaders” in the medical world.

- Are you so sure that ozone is more effective than chemotherapy in the treatment of cancer?

Clearly. As I have mentioned there are some tumors that can be cured with chemotherapy but in the case of patients with advanced cancer, those whose tumors continue to grow despite chemotherapy, I can assure you that if we divided the patients into two groups, one treated with ozone and another one with chemotherapy, we would find the best life expectancy and quality of life in the group treated with ozone. And I am not proposing that we treat ozone as an alternative to chemotherapy but as a complementary treatment.

It has been demonstrated that ozone has a potent germicide effect and that when it liberates oxygen in the tissues it increases the body’s enzymatic anti-oxidant capabilities without oxidative effects. It has also been shown that ozone has a strong analgesic and anti-inflammatory action and balances the immune system, being capable of liberating substances with anti-tumor powers, without secondary effects. Who can believe that a product that does all these things is not really indicated for cancer patients?

- Additionally, the treatment is a lot cheaper, which means that the state would save a lot of money.

True. The savings brought about by using ozone to treat a number of conditions would be tremendous, but that would collide with the interests of multinationals and its defenders within the Health Administration. This is the reason that explains why there are no initiatives to demonstrate through research that ozone and other natural products and treatments with no side effects, which cannot be patented, are beneficial to patients.

- But ozone is not a panacea in cancer treatments…

No it is not. Cancer must be treated in an integral manner. What is evident is that ozone therapy is very beneficial for cancer patients as well as for patients suffering from other illnesses.

- Has any Health Administration (within Spain) shown any interest in listening to the potential benefits of ozone therapies?

No, what’s more, until a short time back, it persecuted and sanctioned those who practiced ozone therapies. The MDs who practice ozone therapies have in fact lived in fear from the Health System inspections. It seems grotesque to me, but to many health inspectors, the fact of extracting blood from a patient, ozonating it and putting it back into their bodies seems like witchcraft. They are incapable of understanding and accepting that in many of the most advanced European countries this is a regular, daily medical practice.

- If the Health Administration behaves in this manner, can we say that it is impossible to carry out a rigorous study that describes the efficacy of ozone therapies in cancer or other illnesses?

That is correct, because no laboratory would finance it and no regional government would do it either. And individuals cannot afford it because it is too expensive. In fact, this is the reason that explains the fact that the studies about ozone that have been published in scientific journals are not taken seriously, because they are not large enough. Nobody would finance large studies if the product or treatment cannot be patented. Today, public health is a business and those who derive an economic benefit from it will undermine any treatment or product that has not been developed according to their norms… knowing that nobody is going to finance it. However, I have to say that Dr. Marques and I recently formed a research group on ozone, GIDO, whose funds have been donated by the Fundación Fabré that presides Juan Angel Regojo. In short, the fact that something has not been “scientifically demonstrated” following the multinationals’ standards does not mean that it doesn’t work.

- Has any of the oncologist associations, or the Spanish Association Against Cancer, or the National Center for Oncological Research ever requested any information about your research and work?

No. None of them. At some point in the past, a person from the Spanish Association Against Cancer from Pontevedra suggested that I give a talk about my work but the person could not get the association to approve his initiative.

- How about any oncologist?

No.


- Do you at least know what they think about ozone therapies? Probably some patients have asked them their opinion about whether or not ozone therapy may work in their case..

In our country, oncologists are very drastic with their patients in terms of them using parallel protocols. Patients are scared to tell them the truth because they don’t want to risk their doctors getting angry at them and stop the follow up tests. It is my understanding that a minority of patients has mentioned what we do to their oncologists and the general answer is along the lines of “it’s your money, but it will not work”. They criticize ozone therapy without knowing it and as if it was not a medical practice, as if those of us who use it were charlatans, not certified, professional MDs. What is more, some patients have received terribly angry responses from their oncologists, who stopped the chemotherapy on the patients when they confessed that they were doing ozone treatments at the same time. It is incredible, but many doctors think that the treatments consist on having the patient breath ozone! The level of ignorance about ozone therapies is incredible.

- In the face of these circumstances, do you really think that there is a future for Ozone Therapies?

Without a doubt. I have no doubt that its use will become prevalent sooner or later because ozone is a powerful medical tool that allows doctors to treat a number of pathologies, saving numerous surgical interventions and generating huge drug savings to patients, the state and the medical insurance companies. What is more, ozone helps humans age healthily and, at the least, to be able to have a better quality of life while suffering an illness.

I am persuaded of the fact that in the future, there will be ozone generators in every neighborhood. This would be feasible and cheap to implement already today.

With regards to cancer, ozone will become a necessary therapy in any stage of the illness and the use of intraperitoneal ozone will be viewed as a basic procedure. Our work now is to establish with as much accuracy as possible the treatment protocols. The Spanish government should bet on these therapies. Now is the moment to do it.

Antonio F. Muro


 

 

 



Ultima actualización (Viernes 09 de Mayo de 2014 22:31)

 

Utilidad de la Ozonoterapia en Cáncer y otras patologías

 

Pinche en este link para leer el artículo completo

http://ozonoterapiasalud.com/pdf/perez-olmedo-ozono-cancer-discoverysalud-2013.pdf

 

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Ultima actualización (Martes 04 de Febrero de 2014 14:57)

 

Integrative Cancer Therapies

Ultima actualización (Jueves 17 de Enero de 2013 11:44)

 

ozono en el daño a órganos de ratas inducido por la radiación ionizante

Efectos del preacondicionamiento con ozono en el daño a órganos de ratas inducido por la radiación ionizante

Fatma Ayca Gultekin*, Bekir Hakkan Bakkal (2), Berrak Guven(3), Ilhan Tasdoven(1), Sibel Betkas(4), Murat Can(3) and Mustafa Comert(1)

1 Bulent Ecevit University, School of Medicine, Department of General Surgery, Kozlu, Zonguldak 67600, Turquia

2 Bulent Ecevit University, School of Medicine, Department of Radiation Oncology, Kozlu, Zonguldak 67600, Turquia

3 Bulent Ecevit University, School of Medicine, Department of Biochemistry, Kozlu, Zonguldak 67600, Turquia

4 Bulent Ecevit University, School of Medicine, Department of Pathology, Kozlu, Zonguldak 67600, Turquia

*Correspondencia autor. Tel: +90-372-2613201; Fax +90-372-2610155; Emai: Esta dirección electrónica esta protegida contra spambots. Es necesario activar Javascript para visualizarla  

RESULTADOS

Los niveles de AST Y ALT en plasma, que fueron usados como índice de daño hepático y de daño generalizado a los tejidos, fueron significativamente más elevados en los grupos TBI a las 6 o 72 h post radiación comparados con el grupo control (p= 0.001 Y P<0.001, respectivamente; Fig 1ª y 1B), mientras que el POO previno la elevación de AST en los grupos 4 y 5 (P=0.001); Fig. 1ª), y de ALT en el grupo 5 (P<0.001; Fig. 1B). En los grupos 2 y 3 (salino + TBI), los niveles de TNF alfa fueron significativamente más elevados (p<0.001) comparados con el grupo control, mientras que la TBI subió los niveles de TNF alfa el los salino tratados, en los POO+TBI descendió comparado con el grupo control (Tabla 1). El MDA es un índice de daño hepático asociado a Lipoperoxidación. Comparado los grupos salino tratados con el grupo control los valores de MDA fueron significativamente más elevados en estos grupos (P=0.001 y p<0.001 respectivamente), sin embargo en los grupos POO+TBI el tratamiento con ozono previno la peroxidación en ambos tejidos (P=0.001 y P<0.001 respectivamente, Tabla 1). La actividad de la SOD indica la generación de estrés oxidativo, una rápida respuesta de descenso de la SOD se dio en los grupos salino tratados+TBI tanto a las 6 como a las 72 h siguientes a la TBI comparado con el grupo control (P<0.001, Tabla 1). Sin embargo el POO previno las alteraciones de la SOD en todos los tejidos (P<0.001, Tabla 1).

En el examen histopatológico, no hubo anormalidades en hígado e íleon en el grupo control (Grupo 1, Fig. 2ª y 3ª). Dilatación de sinusoides, congestión y dilatación de venas centrales así como un mínimo infiltrado mononuclear inflamatorio en las tríadas portal se encontraron en los grupos salino + TBI a las 6 h post TBI (grupo 2) y mucho más acusada en el grupo 3 (Grupo 3, Fig 2 C), también se encontró una moderada degeneración hepatocelular en este grupo. En los grupos 4 y 5 estos hallazgos fueron mucho más reducidos y prácticamente semejantes al grupo control (Fig 2D y 2E). Degeneración focal y pérdida de vellosidades en el epitelio e infiltrado inflamatorio en la lámina propia se observaron en la mucosa íleal en el grupo salino analizado a las 6 h (Grupo 2, Fig 3B). Desordenada estructura de las vellosidades, degeneración focal y pérdida de las vellosidades epiteliales, congestión subepitelial y marcado infiltrado inflamatorio mononuclear en la lámina propia fueron notables en el grupo salino a las 72 horas (Grupo 3, Fig. 3C). En los grupos POO+TBI a las 6 h (Grupo 4, Fig 3 D), el infiltrado inflamatorio fue mucho más reducido comparado con el Grupo 2 (salino a las 6 h). Regular estructura de vellosidades, abundantes copas celulares en el epitelio y reducido infiltrado en la lámina propia ocurrió en el grupo 5 (POO a las 72 h) (Fig. 3E). En este grupo no hubo congestión subepitelial.

 

Fig. 1. Niveles de (A) AST y (B) ALT en muestras de suero del grupo control y del grupo tratados con salino y ozono y decapitados a las 6 y 72 h después de la irradiación (TBI). Cada grupo se compone de 6 ratas. *P=0.001, +P<0.001: comparado con grupo control; **P=0.001, ++P<0.001: comparado con grupo salino.

 

Tabla 1. Niveles de MDA (nmol/g) y actividad SOD (U/g) en tejido hepático e íleon y nivel de TNF alfa en suero en control, tratados con suero salino y tratados con ozono más TBI (decapitados para estudio a las 6 y 72 h después del TBI –total body irradiation-), Cada grupo se compone de seis ratas.

 

CONTROL

GRUPOS TBI (Irradiación total del cuerpo)

 

6 horas

72 h

 

Salino tratados

Ozono tratados

Salino tratado

Ozono tratados

 

Grupo 1

Grupo 2

Grupo 3

Grupo 4

Grupo 5

 

Íleon

MDA (nmol/g)

1,76+-0.4

5.6+-0.48*

2.35+-0.38¨

6.16+-0.63*

2.78+-0.54¨

SOD (U/g)

24,09+-1.24

7,67+-0.39*

18,26+-2.39¨

9,25+-1,09*

24,97+-1,39¨

Hígado

MDA (nmol/g)

4,33+-0.12

6,42+-0.28**

4,42+-0.12¨¨

6,72+-0.21**

4,16+-0.56¨¨

SOD (U/g)

42,69+-0.70

20,04+-2,32*

37,60+-3,16¨

20,24+-0,78*

46,31+-2.38¨

Suero

TNF alfa

(pg/ml)

20.96+-0.70

28.66+-0.40*

19.51+-0.62¨

27.03+-0.77*

17,91+-0.47¨

*P<0.001, **P=0.001 comparado con grupo control; ¨P<0.001, ¨¨P=0.001 comparado con grupo salino+TBI

Fig. 2. Efectos del POO en la morfología del hígado de ratas. (A) Grupo control ; (B) Grupo tratado con suero salino Y TBI estudiado a las 6 h: congestión y dilatación de sinusoides (flecha gruesa) y vena central (flecha delgada); (C) Igual que B pero estudiado a las 72 h: aberrante dilatación y congestión en sinusoides (flecha gruesa) y venas centrales (flecha delgada) y moderada degeneración hepatocelular; PPO y TBI estudiados a las 6 h (D); y (E) a las 72 h: leves cambios con respecto al grupo control (A), especialmente menores con respecto a los grupos tratados con suero salino.

Discusión

La radioterapia es un pilar fundamental en el tratamiento del cáncer, se estima que un 50% de pacientes con cáncer reciben y obtienen beneficio de la radioterapia. Aunque es una herramienta muy común y útil, la especial radiosensibilidad de los tejidos adyacentes al tumor irradiado limita la ganancia terapéutica (22). La radiación ionizante provoca la formación de ROS por hidrolisis radiolítica de las moléculas de agua y los ROS son los causantes del estrés oxidativo y consecuente daño tisular. Los ROS inducen alteraciones en moléculas y estructuras vitales de la célula, como en el DNA, lípidos, proteínas y membranas (24).

No obstante, la radiación ionizante disminuye la capacidad antioxidante del organismo dando como resultado un desequilibrio entre pro-oxidantes y antioxidantes (8,9). Hemos hipotetizado que si el estrés oxidativo inducido por la radiación ionizante es el origen del daño a los tejidos luego un tratamiento antioxidante exitoso pudiera retrasar o prevenir la aparición de estos daños.

La terapia con ozono tiene efectos beneficiosos para varias enfermedades, así como en quemaduras causticas de esófago, pie diabético, cistitis inducida por radiación (26,30). Puede ser administrado vía tópica, rectal, sanguínea, intraperitoneal, oral, intramuscular, etc. Además, recientemente se ha descubierto que el ozono es capaz de inducir una adaptación al estés oxidativo y promover un preacondicionamiento oxidativo a través de un aumento y preservación de los sistemas endógenos antioxidantes en modelos animales de hapatotoxicidad (como el inducido por CCL4). También puede proteger frente al daño hepato-renal provocado por la isquemia-reperfusión (15,17). Ajamieh y col. Demostraron que los tratamientos con ozono en número y dosis controladas confieren protección frente diferentes procesos fisiopatológicos mediados por ROS (especies reactivas del oxígeno)(17,24). Llaman a este fenómeno Preacondicionamiento con oxígeno-ozono (POO). El POO protege al anfitrión del daño por ROS e induce una mejora de equilibrio prooxidante-antioxidante y consecuentemente preserva el estado redox celular.

En este estudio, específicamente investigamos si el POO pudiera tener efectos protectores contra el daño oxidativo provocado por la radiación ionizante en el hígado, íleon y el suero. Nuestros resultados muestran que la TBI (irradiación total del cuerpo: total body irradiation) de ratas con una dosis de 6 Gy causa un aumento de la lipoperoxidación en hígado e íleon demostrada por los niveles de MDA (malondialdehído), que es un buen indicador de la degradación de los lípidos por peroxidación (31). Se ha informado que la exposición a radiación de alta energía (Co-60) de todo el cuerpo de las ratas provoca daño tisular en varios tejidos y un incremento de la peroxidación lipídica evaluada a las 2, 12 y 72 horas post irradiación (8,9). Así, el daño inducido por la radiación puede provocar efectos adversos en la salud entre horas a semanas y los efectos retardados pueden ser observados muchos meses después de la exposición (23). En nuestro estudio comparamos el grupo control, los niveles de MDA en tejidos hepáticos e ileales, a los grupos tratados con suero salino + IR a las 6 y 72 horas post-radiación (grupos 2 y 3) existiendo un significativo incremento de los niveles de MDA, tanto a las 6 como a las 72 h. los niveles de MDA registrados fueron similares (Tabla 1). Con el POO previo a la radiación se encontró un descenso de la lipoperoxidación. Parece probable que el ozono aminora el daño oxidativo inducido por la radiación en parte por activación de rutas metabólicas que mantienen equilibrado el balance redox. Igualmente, se ha demostrado que el POO protege el hígado y el riñón de ratas expuestas a isquemia-reperfusión (15,16). En el estudio de Ajamieh y col., ambos preacondicionamientos, isquémicos y POO, produjeron similares efectos protectores en la lesión por reperfusión tras isquemia hepática (15). Por otro lado, Guven y col., demostraron que la terapia con ozono reduce los niveles de MDA en el íleon en un cachorro con enterocolitis necrotizante (18). Nuestros resultados están de acuerdo con los estudios previos que encuentran que la administración de ozono atenúa la oxidación de lípidos y proteínas en el daño de hígado e íleon mediados por los ROS (15,16,18). La lipoperoxidación puede ocasionar varias discapacidades el la función de la membrana por aumento de su permeabilidad y la oxidación de las proteínas de membrana (29). En el presente estudio, la TBI indujo un significativo incremento de la actividad de las enzimas hepáticas ALT y AST. Es aumento en el suero de la actividad de las aminotransferasas por radiación puede ser atribuido al daño en la membrana de las células de los hepatocitos por excesiva producción de ROS, que pueden causar la fuga de enzimas citosólicas fuera de la célula aumentando la actividad aminotransferasa en el suero sanguíneo. El POO restaura significativamente la actividad enzimática (AST Y ALT) debido a la capacidad de preservar el estado redox de la célula y asegurando que los aldehídos tóxicos no se formen.

En el presente estudio, los sistemas antioxidantes del hígado e íleon fueron claramente afectados por la TBI. Una considerable reducción de la actividad de la SOD en el grupo tratado con suero salino más TBI. Pudiera ser debido al aumento en la utilización de los sistemas antioxidantes en un intento de controlar la excesiva producción de ROS generados por la radiación. El POO incrementa la actividad total de la SOD en hígado e íleon comparado con el grupo suero salino + TBI. Nuestros resultados están de acuerdo con otros estudios reportados de incremento de actividad de la SOD, CAT y peroxidasas después de repetidas atóxicas dosis de exposición al ozono (13,17). El POO fue aparentemente capaz de aumentar los sistemas antioxidantes, y el efecto del ozono sobre el hígado e íleon fue similar al efecto sobre los sistemas antioxidantes. El grupo tratado con ozono menor degeneración hepatocelular que el grupo tratado con suero salino. Más aún, el infiltrado inflamatorio en la lámina propia de íleon se redujo en el grupo POO. El ozono parece reducir el daño por restauración del balance redox.

El daño a los tejidos iniciada por la radiación esta asociada con la producción de importantes mediadores biológicos, incluyendo citokinas (30), que perpetúan la inflamación y procesos de fibrosis asociados a la radiación (31). Estudios clínicos y experimentales han demostrado que cualquier sustancia nociva puede activar macrófagos y monocitos que, a su vez, secretan citokinas tales como Interleukina-1 (IL-1) y TNF-alfa (32,33). Como se evidencia en el presente estudio, la TBI resulta en un incremento en el suero de TNF-alfa, indicando el papel de esta citokina en la toxicidad inducida por la radioterapia, mientras que el POO deprime la respuesta del TNF-alfa. Así, parece probable que los efectos inhibidores del ozono sobre el TNF-alfa en el suero de ratas que recibieron TBI es una consecuencia de la estimulación de las defensas antioxidantes inducidas por el POO. Recientemente, Zamora y col., analizaron los efectos del POO sobre los niveles del TNF-alfa en el suero y tejido hepático en un modelo de shock endotóxico (33). De acuerdo con nuestros resultados, el POO ejerce efectos inhibitorios sobre la producción de TNF-alfa.

Numerosos estudios demuestran que el POO es capaz de provocar una adaptación al estrés oxidativo (13-19, 26-28). Nuestro estudio confirma los hallazgos previos, el ozono ejerce influencia sobre el equilibrio antioxidante-prooxidante al preservar el estado redox celular debido al incremento del sistema endógeno enzimático antioxidante. Los mecanismos que subyacen son todavía desconocidos, varios estudios intentan determinarlos. En el estudio de Leon y col., (17), el POO provee protección hepática contra la intoxicación por CCL4. Este resultado esta sustentado por varios hallazgos tales como el incremento de la actividad SOD, CATALASA Y PEROXIDASAS después de la exposición crónica al O3. Las plantas también pueden expresar una respuesta protectora tras la exposición al ozono, sugieren que varios organismos vivos expuestos crónicamente al ozono tienen la opción de programar su muerte o bien reaccionar para sobrevivir regulando sus defensas antioxidantes para reajustar el equilibrio redox (34,35). Por otro parte, en pacientes, se observó que un transitorio estrés oxidativo tal como el que sucede durante un ciclo de tratamiento con ozono (autohemoterapia) puede inducir un estado de tolerancia caracterizado por una simultánea sobre expresión de SOD. G-6-P deshidrogenasa y posiblemente una reducción de los niveles de productos reactivos al ácido tiobárbiturico (TBARS) en plasma (13,14,27). Otro estudio evaluó los efectos del POO en la generación de NO y el balance redox celular en un modelo experimental en ratas sometidas a isquemia-reperfusión hepática (36) sugieren que el POO pudiera primero activar los genes asociados a la expresión de la oxido nítrico sintetasa (NOS), que promueve la formación de NO en las concentraciones requeridas para proteger contra el daño por isquemia-reperfusión hepática. Igualmente, Punjabi y col. (37) y Pendino y col. (38) que la exposición al ozono causa producción de NO en macrófagos y células tipo II de ratas, mientras Haddad y col. (39) demostraron que induce en ratas la expresión de iNOS (Oxido nítrico sintetasa inducible). Más recientemente, la aplicación intrarectal de ozono reduce las ROS por estimulación y/o preservación de los sistemas antioxidantes endógenos en modelos experimentales de isquemia-reperfusión en hígado y riñón, respectivamente (17,39,40). Finalmente, Martínez y col., evaluaron la eficacia terapéutica del ozono en pacientes con pie diabético, y concluyeron que uno de los mecanismos que subyace pudiera la inducción de la SOD a través de la estimulación de la expresión de genes de la SOD. Estudios previos utilizaron la isquemia-reperfusión para evaluar los efectos del POO en el daño a tejidos, mientras que no nuestro estudio es el primero en demostrar el efecto protector del POO en el daño oxidativo a tejido hepático e íleal inducido por la radiación, así como a mejorar los niveles de TNF alfa en el suero. No obstante, nuestro estudio no determinó los mecanismos que subyacen en el POO, está ha sido la principal limitación, sí demuestra los efectos del tratamiento con ozono en el daño a órganos inducido por la radiación. Podríamos haber aclarado si el ozono pudiera proteger los enzimas antioxidantes frente a la radiación o lo que hace es inducir la expresión de genes de enzimas antioxidantes. Sin embargo, estudios previos proporcional algunas explicaciones sobre los mecanismos subyacentes en los tratamientos con ozono en algunos modelos de experimentos. Por lo tanto, diseñamos el estudios de acuerdo a los hallazgos previos, no evaluamos los mecanismos que subyacen al tratamiento con ozono en los tejidos sometidos a TBI.

En resumen, la radioprotección observada con POO es atribuida a un incremento de las defensas antioxidantes endógenas y a una inhibición de la lipoperoxidación. Sin embargo, más estudios se necesitan para dilucidar los mecanismos que justifican los efectos beneficiosos del POO en los tejidos sometidos a radiación

Bibliografía.Referencias

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ref-9

Ultima actualización (Jueves 08 de Noviembre de 2012 19:47)

 

Ozono intraperitoneal en el Carcinoma de células escamosas cutáneo

Os dejo este artículo (esta en ingles) del trabajo realizado en Algeciras Cadiz por el veterinario Dr. Miguel Hormigo de la clinica "El Estrecho" en el cual ha colaborado estrechamente el Dr. Perez Olmedo.

Enlace: http://www.theolivepress.es/spain-news/2012/03/30/pawfect/

 

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