Dr. Alvin Philipose DC/ Nitin Sawheny MD
Prolotherapy Injections Specialist Near Me in Oklahoma City, OK

405.848.7246
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Discover the Power of Ozone Therapy in Oklahoma City

Are you looking for an innovative, natural approach to managing pain, boosting your immune system, or addressing chronic conditions? At Venturis Regenerative Medicine in Oklahoma City, we specialize in ozone therapy—an advanced treatment that has helped countless patients reclaim their health and vitality.

What is Ozone Therapy?

Ozone therapy is a medical treatment that uses ozone (a highly reactive form of oxygen) to stimulate your body’s natural healing processes. By introducing ozone into your bloodstream or tissues, this therapy enhances oxygen delivery, reduces inflammation, and promotes cellular repair.

Benefits of Ozone Therapy

Ozone therapy offers a wide range of benefits for patients dealing with various health conditions, including:

1.Pain Management:

•Relieves chronic pain caused by conditions such as arthritis, fibromyalgia, and back pain.

•Reduces inflammation and accelerates healing in injured tissues.

2.Immune System Boost:

•Strengthens your body’s defense mechanisms to fight infections and autoimmune disorders.

3.Improved Energy Levels:

•Increases oxygen utilization, helping you feel more energetic and focused.

4.Detoxification:

•Supports your body’s natural detox processes, removing harmful toxins and free radicals.

5.Enhanced Healing:

•Speeds up recovery from injuries, surgeries, and chronic wounds.

Conditions Treated with Ozone Therapy

At Venturis, we’ve successfully treated patients with:

•Chronic pain and inflammation

•Autoimmune conditions (like rheumatoid arthritis and lupus)

•Chronic fatigue syndrome

•Lyme disease

•Migraines

•Sports injuries

Why Choose Venturis Regenerative Medicine?

Venturis is Oklahoma City’s premier clinic for ozone therapy and regenerative medicine. Here’s what sets us apart:

Expert Care: Our team is highly experienced in providing safe, effective ozone treatments tailored to your needs.

Cutting-Edge Technology: We use the latest medical equipment to ensure precision and comfort during your therapy sessions.

Patient-Centered Approach: Your health and well-being are our top priorities. We take the time to understand your concerns and create a personalized treatment plan.

What to Expect During an Ozone Therapy Session

Your first visit will include a consultation to determine the best approach for your unique needs. Depending on your condition, ozone therapy may be delivered through:

IV Infusion: Directly into your bloodstream for systemic benefits.

Injection: Targeted delivery to specific joints or muscles.

Topical Application: For wound healing and skin conditions.

Each session typically lasts 30-60 minutes, and most patients experience noticeable improvements after just a few treatments.

Testimonials from Our Patients

“I was struggling with chronic back pain for years. After trying ozone therapy at Venturis, I’ve finally found relief! The staff is amazing, and I feel like a new person.” – Sarah M.

“The ozone treatments at Venturis have helped me manage my autoimmune condition without relying on harsh medications. I’m so grateful for their care.” – John D.

Take the First Step Toward Better Health

Ozone therapy is transforming lives across Oklahoma City, and it can do the same for you. Whether you’re seeking relief from chronic pain or looking to improve your overall health, our team at Venturis Regenerative Medicine is here to help.

Contact Us Today

📍 Address: 6500 N. Meridian, Oklahoma City, OK 73116

📞 Phone: 405-848-7246

🌐 Website: venturisclinic.com

Ready to experience the benefits of ozone therapy? Schedule your consultation today and discover why Venturis is the trusted choice for regenerative medicine in Oklahoma City.

Chemotherapy and radiation may be life-saving treatments, but they often come with intense physical side effects, leaving patients feeling drained and depleted. In fact, studies show that up to 70% of cancer survivors face long-term issues like fatigue, reduced immunity, and oxidative stress following their treatments. At Venturis Clinic in Oklahoma City, we believe your post-cancer journey deserves just as much attention as your treatment journey.

For patients looking to recover, rebuild, and reclaim their vitality, innovative therapies like ozone infusions, hyperbaric oxygen therapy, and high-dose vitamin C can make a remarkable difference. These therapies don’t just manage symptoms; they promote healing from within, helping your body repair itself more effectively. Here, we’ll break down each of these treatments, explaining how they work and the unique benefits they can provide on your road to recovery.

The Challenges of Post-Cancer Recovery

Cancer treatments, while powerful, can leave behind a significant footprint on your health. Radiation and chemotherapy may trigger persistent inflammation, increase oxidative stress, weaken immune function, and drain your energy. This can make daily activities feel like mountains to climb, and for many, recovery doesn’t happen as fast as they’d like.

The good news? Modern integrative therapies offer an approach that works with your body, helping it recover more naturally. Our goal at Venturis Clinic is to support you with therapies designed to repair and restore, so you can regain your strength and vitality.

Ozone Therapy: Recharging Your Cells and Fighting Inflammation

What It Is: Ozone therapy involves infusing medical-grade ozone—a highly reactive form of oxygen—into the bloodstream. This extra oxygen boosts your body’s ability to repair itself by increasing oxygenation and reducing inflammation.

How It Helps Post-Cancer Recovery: Radiation and chemotherapy can deplete the body’s cells and reduce oxygen levels. Ozone therapy delivers a concentrated oxygen boost, which not only recharges your cells but also helps neutralize toxins and reduce harmful inflammation. This can be especially beneficial for improving energy levels, immune function, and cellular repair.

What to Expect: Ozone infusions are minimally invasive, with each session lasting about 30–60 minutes. During this time, the ozone mixture is introduced into the bloodstream, where it gets to work supporting cellular health and recovery.

Hyperbaric Oxygen Therapy (HBOT): Boosting Oxygenation and Accelerating Healing

What It Is: Hyperbaric oxygen therapy involves breathing 100% oxygen in a pressurized chamber, allowing your lungs to absorb higher levels of oxygen than usual. This therapy delivers oxygen directly to damaged tissues and supports rapid healing.

How It Helps Post-Cancer Recovery: Post-chemotherapy and radiation, tissues and cells may struggle to repair due to reduced oxygen availability. HBOT helps overcome this by delivering concentrated oxygen, which can stimulate the release of growth factors and stem cells to repair damaged tissues. Studies have shown HBOT can be particularly beneficial for managing radiation-induced tissue damage, chronic fatigue, and brain fog, common concerns for many cancer survivors.

What to Expect: During HBOT sessions, you relax in a specialized chamber while breathing pure oxygen. The treatment typically lasts 60–90 minutes, and most people experience a noticeable boost in energy and mental clarity after a few sessions.

High-Dose Vitamin C Infusions: Strengthening Immunity and Combating Oxidative Stress

What It Is: High-dose vitamin C therapy involves infusing a therapeutic amount of vitamin C directly into your bloodstream, bypassing the digestive system for maximum absorption.

How It Helps Post-Cancer Recovery: Chemotherapy and radiation create a high level of oxidative stress, which can damage healthy cells. Vitamin C is a potent antioxidant, helping to neutralize free radicals and protect your cells. Additionally, high doses of vitamin C have been shown to boost the immune system, enhance collagen production (supporting tissue repair), and even help with post-treatment fatigue.

What to Expect: Each vitamin C infusion typically lasts around an hour, and it’s administered in a comfortable setting. Unlike oral supplements, IV vitamin C allows you to receive therapeutic doses that support recovery without taxing your digestive system.

Combining Therapies for Optimal Recovery

At Venturis Clinic, we take a personalized approach to your post-cancer recovery. We often recommend combining ozone, hyperbaric, and vitamin C therapies to maximize the benefits. Here’s why:

Synergy of Treatments: By combining these therapies, we can target recovery on multiple fronts: re-oxygenating tissues, reducing inflammation, and supporting immunity.

Comprehensive Healing: These therapies work together to promote holistic healing, helping you regain strength, energy, and resilience more effectively.

Personalized Care: Every patient’s recovery journey is unique. Our team will work with you to create a treatment plan tailored to your specific needs, ensuring you get the best possible support for your recovery.

What Patients Are Saying

Many of our patients have found new energy and vitality after integrating these therapies into their recovery routine. Here’s what one patient shared:

“After chemo, I was exhausted and felt like I couldn’t bounce back. I tried the ozone and vitamin C infusions at Venturis Clinic, and within a few weeks, I noticed a huge difference. My energy levels were up, and I felt like I was finally getting my life back.”

Ready to Support Your Recovery with Innovative Therapies?

If you’re looking for ways to regain strength and improve your quality of life after cancer treatment, consider exploring these therapies at Venturis Clinic. Our team in Oklahoma City is here to help you reclaim your health with therapies designed to support natural recovery and resilience. Schedule a consultation with us today, and let’s discuss how ozone infusions, hyperbaric oxygen therapy, and high-dose vitamin C can support your post-cancer journey.

The journey to recovery can feel overwhelming, but you don’t have to navigate it alone. With the right support, your body can begin to rebuild and thrive. At Venturis Clinic, we believe in therapies that empower your natural healing processes. Reach out to us and learn how we can help you regain your strength, health, and vitality.

All-Inclusive Guide to Autohemotherapy: Essential Information

People are constantly searching for alternative therapies that support the body's inherent healing capacity in their pursuit of well-being. The intriguing and becoming more well-liked therapy known as autohemotherapy is drawing interest due to its ability to improve vitality and health. We'll go into the specifics of autohemotherapy in this extensive guide, answering any questions you may have about this fascinating healing modality.

Knowing About Autohemotherapy:

**1. Foundations:**
Reinfusion of a patient's own blood—which has undergone some sort of modification or treatment—into the body is known as autohemotherapy. Numerous physiological reactions are triggered by this process, which might have a favorable effect on one's general health and well-being.

**2. Distinct Methods:**
There are several variations of autohemotherapy, and each has special advantages. People can select a technique that suits their interests and health goals from a variety of possibilities, such as major autohemotherapy, UV light therapy, and Ozone Autohemotherapy, which involves treating blood with medical-grade ozone.

**3. Increased Oxygenation:**
The rise in blood oxygen levels is one of the main advantages of autohemotherapy. This therapy enhances cellular activity and helps the body function at its peak by enhancing oxygenation.

**4. Modulation of the Immune System:**
Immune system modulation has been associated with autohemotherapy, which strengthens the body's defense mechanisms. Because of this, it's a very appealing choice for people who want to boost their immunity against diseases and infections.

What to anticipate:

**1. Professional Consultation:**
It's important to speak with a healthcare provider before beginning autohemotherapy. They will review your goals, evaluate your medical history, and choose the best course of action based on your particular requirements.

**2. Therapy Meetings:**
The chosen method and the specific health conditions of each patient may influence the frequency and length of Autohemotherapy sessions. Most people indicate that their sessions are generally well-tolerated, with only minor discomfort.

**3. Possible Advantages:**
Enthusiasts of autohemotherapy have documented a number of advantages, such as heightened vitality, enhanced immunity, and overall wellbeing. But it's important to remember that every person will react differently.

### Safety Points to Remember:

Professional Oversight: **1.
Only qualified medical personnel should oversee the administration of autohemotherapy. Unsupervised therapies or do-it-yourself methods carry potential dangers and should be avoided.

**2. Personalized Approach:** Reactions to autohemotherapy can differ between individuals and health situations. Working with medical experts who can customize the treatment plan to meet your unique needs is therefore essential.

 

For those looking for a natural and comprehensive approach to wellbeing, autohemotherapy appears to be a viable option. Through comprehension of the fundamentals, investigation of various methods, and assessment of safety issues, people can make knowledgeable choices on the incorporation of Autohemotherapy into their health journey. To ensure a safe and successful experience, like with any health-related decision, consulting with healthcare specialists is essential. Take advantage of autohemotherapy's potential advantages and set out on a journey to improved health and vigor!

Accepting Well-Being: Exposing the Advantages of Ozone Autohemotherapy

People are always looking into cutting-edge therapies that use the power of nature in their quest for holistic health and wellness. Ozone Autohemotherapy is one such therapy that is gaining popularity. It is a method that involves injecting ozone into one's own blood for a host of health advantages. We'll explore the intriguing field of ozone autohemotherapy in this blog and see how it may be able to open the door to a happier, healthier existence.

Recognizing Ozone for Autohemotherapy: A little portion of a patient's blood is removed during autohemotherapy, which is a minimally invasive technique. The blood is then treated with medical-grade ozone and reintroduced into the body. This process promotes general well-being by inducing a variety of physiologic reactions.

Enhanced Oxygenation: The molecule ozone, which is made up of three oxygen atoms, has the amazing capacity to raise the body's oxygen content. Ozonated blood supports cellular function and vitality by delivering increased concentrations of oxygen to tissues and organs when it enters the bloodstream.

Ozone: Enhanced Immune System It is well known that autohemotherapy modulates the immune system, increasing its effectiveness in fending against infections and illnesses. Ozone helps the body create a stronger barrier against infections by stimulating immune cells, which in turn strengthens the body's inherent healing capacity.

Detoxification: The body may eliminate toxins and metabolic waste products with the help of ozone's potent detoxifying qualities. The liver and kidneys are supported during this detoxification process, which also fosters a healthier, more hygienic internal environment.

Anti-Inflammatory Effects: A number of health problems are preceded by chronic inflammation. Ozone contributes to a more balanced and harmonious body state by having anti-inflammatory qualities that can help reduce inflammation and lower the risk of inflammatory-related illnesses.

Ozone Promotes Better Circulation There is evidence that autohemotherapy promotes better blood circulation. This treatment may improve the transport of nutrients and oxygen to cells, facilitating tissue regeneration and repair, by increasing blood flow.

Pain management: Ozone autohemotherapy may be able to provide relief for people with long-term pain issues. The analgesic and anti-inflammatory properties of the therapy can help control pain and enhance quality of life in general.

 2017 Jul-Sep; 7(3): 212–219.
Published online 2017 Oct 17. doi: 10.4103/2045-9912.215752
PMCID: PMC5674660
PMID: 29152215

Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility

Associated Data

Supplementary Materials

Abstract

The use of ozone (O3) gas as a therapy in alternative medicine has attracted skepticism due to its unstable molecular structure. However, copious volumes of research have provided evidence that O3's dynamic resonance structures facilitate physiological interactions useful in treating a myriad of pathologies. Specifically, O3 therapy induces moderate oxidative stress when interacting with lipids. This interaction increases endogenous production of antioxidants, local perfusion, and oxygen delivery, as well as enhances immune responses. We have conducted a comprehensive review of O3 therapy, investigating its contraindications, routes and concentrations of administration, mechanisms of action, disinfectant properties in various microorganisms, and its medicinal use in different pathologies. We explore the therapeutic value of O3 in pathologies of the cardiovascular system, gastrointestinal tract, genitourinary system, central nervous system, head and neck, musculoskeletal, subcutaneous tissue, and peripheral vascular disease. Despite compelling evidence, further studies are essential to mark it as a viable and quintessential treatment option in medicine.

Keywords: ozone, ozone therapy, ozone gas, autohemotherapy, oxidative stress, reactive oxidative species, lipid ozonation products, oxidative preconditioning

Introduction

Ozone (O3) gas was discovered in the 1840s, and soon after that, the scientific community began to expand past the notion that it was just another gas of the Earth's atmosphere. Though the migration of O3 into the medical field has taken a circuitous road since the 19th century, its medicinal value is currently controversial despite compelling research. O3 is highly water-soluble inorganic molecule composed of three oxygen molecules. O3's inherently unstable molecular structure, due to the nature of its mesomeric states, tends to make it difficult to obtain high concentrations. O3 will often experience transient reactions with itself or water. Thus, it was initially problematic to achieve desired levels and even more difficult is to assess the therapeutic effects of such a transient state., These mesomeric states create a conundrum within the scientific community. A divide has formed between those who believe the volatile nature of these mesomeric states can foster positive responses and those who are wary of its seemingly dangerous effects.

Despite suspicions, a multitude of O3 therapies have shown substantial benefits that span a large variety of acute and chronic ailments. O3 is currently prevalent in dentistry to treat diseases of the jaw. O3 has also proven itself beneficial as a disinfectant for drinking water and sterilization of medical instruments., The function of O3 shares similarities to that of a prodrug, as it is modified upon reacting with molecules to create more active substrates, thus stimulating an endogenous cascade of responses. On the other hand, it is hard to classify O3 as simply a prodrug, due to its capability to directly interact with phospholipids, lipoproteins, cell envelopes of bacteria, and viral capsids. The physiology of these biological responses is herein discussed.

Despite the various benefits, O3 toxicity and clinical utility depends on the concentration and administration to the appropriate site.,,, One of the major contraindications of O3 therapy is lung inhalation. O3 therapy significantly increases airway resistance without changing the compliance or elastic characteristics of the lung. Additionally, direct contact of O3 with the eyes and lungs is contraindicated because of the low antioxidant capabilities in these specific locations.

Literature Retrieval

A MEDLINE® database search of literature extended from 1980 to 2017 to obtain current information regarding O3 therapy, its routes of administration, and mechanism of action. Subsequently, trials pertaining to the clinical implications of O3 therapy were paired by pathology and anatomical system. The most important points refer to the type of pathology, route of O3 administration, type of research trial, result(s) of the trial, side effect(s), and proposed physiological mechanism(s). Literature retrieval was performed in July 2017 and included the term “ozone therapy” combined with the following search criteria: “routes of administration”, “mechanism of action”, “cardiovascular”, “subcutaneous tissue”, “peripheral vascular disease”, “neurological”, “head and neck”, “orthopedic”, “musculoskeletal”, “gastrointestinal”, and “genitourinary”. We did not formulate any exclusion criteria.

Routes of Administration

O3 therapy combines a mixture of oxygen (O2)-O3, with a diverse therapeutic range (10–80 μg/ml of gas per ml of blood).,, O3 therapy administration is variable based on treatment goals and location of therapy. The first and most popular is O3 autohemotransfusion (O3-Aht). O3-Aht has grown in popularity because it allows for a predetermined amount of blood to be taken and thus, using stoichiometric calculations, a precise concertation of O2-O3 can be infused. This small amount of blood is subjected to O2-O3 ex vivo is then administered to the patient., Extracorporeal blood oxygenation and ozonation are very similar techniques. However, its goal is to obtain higher blood volume than the 200–300 mL seen in O3-Aht.

Other modalities of therapies include direct injection via the intramuscular, intradiscal, and paravertebral site of administration. Rectal insufflation of O3-O3 is another common site of administration. However, insufflation of the nasal, tubal, oral, vaginal, vesical, pleural, and peritoneal cavities have proven to be prudent routes of administration. Cutaneous exposure has also had likely outcomes and can be achieved by sealing the portion of the body in a chamber or bag and insufflating with O3-O3 mixture. Saline with O3-O3 dissolved is used to avoid the risk of embolism when administered intravenously.

Mechanism of Action

Antioxidant capacity

Upon beginning O3 therapy, a multifaceted endogenous cascade is initiated and releases biologically active substrates in response to the transient, and moderate, oxidative stress that O3 induces. O3 can cause this mild oxidative stress because of its ability to dissolve in the aqueous component of plasma. By reacting with polyunsaturated fatty acids (PUFA) and water, O3 creates hydrogen peroxide (H2O2), a reactive oxygen species (ROS). Simultaneously, O3 forms a mixture of lipid ozonation products (LOP). The LOPs created after O3 exposure include lipoperoxyl radicals, hydroperoxides, malonyldialdeyde, isoprostanes, the ozonide and alkenals, and 4-hydroxynonenal (4-HNE). Moderate oxidative stress caused by O3 increases activation of the transcriptional factor mediating nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2's domain is responsible for activating the transcription of antioxidant response elements (ARE). Upon induction of ARE transcription, an assortment of antioxidant enzymes gains increased concentration levels in response to the transient oxidative stress of O3. The antioxidants created include, but are not limited to, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), heme oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), heat shock proteins (HSP), and phase II enzymes of drug metabolism. Many of these enzymes act as free radical scavengers clinically relevant to a wide variety of diseases.

O3, as well as other medical gases, e.g., carbon monoxide (CO) and nitric oxide (NO), has twofold effects depending on the amount given and the cell's redox status. There is a complex relationship between these three medical gases as O3 overexpresses HO-1, also referred to as HSPs of 32 kPa (Hsp32), the enzyme responsible for CO formation, and downregulates NO synthase, which generates NO. Furthermore, O3 upregulates the expression levels of Hsp70 which, in turn, is strictly related to HO-1. O3 may have a developing role in Hsp-based diagnosis and therapy of free radical-based diseases. HO-1 degrades heme, which can be toxic depending on the amount produced, into free iron, CO, and biliverdin (i.e., precursor of bilirubin), a neutralizer of oxidative and nitrosative stress due to its ability to interact with NO and reactive nitrogen species., Recently, it is becoming clear the heat shock response (HSR) provides a cytoprotective state during inflammation, cancer, aging, and neurodegenerative disorders. Given its extensive cytoprotective properties, the HSR is now a target for induction via pharmacological agents. Hsp70 is involved in co- and post-translational folding, the quality control of misfolded proteins, folding and assembly of de novo proteins into macromolecular complexes, as well as anti-aggregation, protein refolding, and degradation. HO isoforms are acknowledged as dynamic sensors of cellular oxidative stress and regulators of redox homeostasis throughout the phylogenetic spectrum. The effect of O3 on these cell activities remains to be evaluated. Hormesis is a potent, endogenous defense mechanism for lethal ischemic and oxidative insults to multiple organ systems. O3 may have a hormetic role in regulating the anti-inflammatory and proinflammatory effects of CO, including prostaglandin formation akin to NO, which has been shown to exert some of its biological actions through the modulation of prostaglandin endoperoxide synthase activity. Inhibiting HO activity prevents CO biosynthesis and its downstream effects; the effect of O3 on this cascade is yet to be determined.

Animal models have postulated the beneficial effects of prophylactic O3 therapy in controlling the age-related effects of oxidative stress., Evidence was provided to show that low O3 dose administration provided beneficial effects on age-related alterations in the heart and hippocampus of rats. Additional research has been performed and provided room for speculation that O3 therapy may provide the mediation of a mechanism involved in rebalancing the dysregulated redox state that accumulates as individuals age. There was an apparent reduction of lipid and protein oxidation markers, lessening of lipofuscin deposition, restoration of glutathione (GSH) levels, and normalization of GPx activity in aged heart tissue. O3 was demonstrated to decrease age-associated energy failure in the heart and hippocampus of rats. Researchers suspect that the improved cardiac cytosolic calcium and restoration of weakened Na+-K+ ATPase activity in the heart and hippocampus, respectively, were associated with the improvements seen.

In hopes of attaining a sense of the possible toxic components of O3 therapy, a study was done to assess the extent of lesions on human hematic mononucleated cells (HHMC), human thymic epithelium, murine macrophages, mouse splenocytes, and B16 melanoma murine cells. A significant finding of the study was that Hsp70 exhibited an O3-induced increase in biosynthesis in HHMC. Hsp70s are synthesized in response to thermal shock and other stressing agents to cope with the damage that stimulates their biosynthesis. Additionally, they stimulate several immune system responses in lymphocytes and macrophages. The study provided evidence that O3 is a stressing agent capable of upregulating the biosynthesis of Hsp70, without toxicity to membranes. However, the membranes of macrophages are highly resistant to the possible toxicity of O3 at high concentrations; HHMC is less resistant at the high end of the spectrum. The statement above should not discount the effectiveness of O3 as a therapy because Hsp70s are induced in HHMCs without lesions up to 20 μg/mL— a typical dose given in O3-AHT.

Cisplatin (CDDP), a treatment used in a variety of cancers has been observed to have nephrotoxicity in 25% of the patients as a side effect. The occurrence of this nephrotoxicity is thought to be secondary to the free radical generation and the inability of ROS scavengers to ameliorate these molecules, leading to acute renal failure. O2-O3 therapy was used to increase the antioxidant capacity of rats exposed to CDDP and compared to control groups. Serum creatine levels were significantly reduced compared to control groups, illustrating the decreased nephrotoxicity indirectly in the rats with CDDP and O2-O3 therapy. In addition to attenuating the nephrotoxicity, O2-O3 therapy also restores the levels of antioxidant defense constituents (GSH, SOD, CAT, and GSH-Px), which are usually decreased by CDDP. Also, thiobarbituric acid reactive substances (TBARS) were reduced, which is a marker of lipid peroxidation in the kidney.,

Additional human studies examined the beneficial effects of O3 therapy employed via O3-AHT, in conjunction with coenzyme Q10, administered orally. The study evaluated SOD levels, a powerful antioxidant and catalase enzyme, an additional antioxidant enzyme in a control group, a group of O3 therapy by itself, and O3 therapy combined with Q10. Evidence has implied that SOD was significantly increased and catalase enzyme insignificantly increased in the O3 + Q10 group when compared to the control group. Malondialdehyde, a product of lipid peroxidation, is an indicator of oxidative membrane damage. Malondialdehyde levels were significantly decreased concentrations in the O3 + Q10 group when compared to the control group. Taken together, this study provides evidence of the beneficial effects of O3 therapy in combination with Q10 in combatting and the prevention of damage elicited by oxidation.

Multiple studies have provided evidence that O3 therapy increased activation of the Nrf2 pathway via the induction of moderate oxidative stress., By doing so, a transient increase in H2O2 and LOPs enhances the number of antioxidants and therefore can be used for a longer time frame to re-establish the balance of the redox system. Additionally, the creation of these antioxidant enzymes has effects, not only at the level of O3 radical metabolism, but on the whole body.,

Researchers have argued that knowing the total antioxidant status and plasma protein thiol group levels of a blood sample are indicators of the precise amount of O3 required to optimize treatments. By developing more accurate antioxidant status indicators, an individual treatment would achieve the correct dosage on a day and case basis.,, Systems have been proposed to have a more precise measurement of the redox state of a patient to achieve this goal. One system proposes simultaneously measuring different biological markers in the blood such as GSH, GPx, GST, SOD, CAT, conjugated dienes, total hydroperoxides, and TBARS. Using an algorithm, information can be gathered about the total antioxidant activity, total pro-oxidant activity, redox index, and grade of oxidative stress. Systems like this can provide insights to the correct dosage and response to O3 therapy based on oxidative stress levels seen in the patient.,,

Vascular and hematological modulation

O3 is a stimulator of the transmembrane flow of O2. The increase in O2 levels inside the cell secondary to O3 therapy makes the mitochondrial respiratory chain more efficient. In red blood cells, O3-AHT may increase the activity of phosphofructokinase, increasing the rate of glycolysis. By enhancing the glycolytic rate, there is an increase in ATP and 2,3-diphosphoglycerate (2,3-DPG) in the cell. Subsequently, due to the Bohr effect, there is a rightward shift in the oxyhemoglobin dissociation curve allowing for the oxygen bound hemoglobin to be unloaded more readily to ischemic tissues. Combined with the increase in NO synthase activity, there is a marked increase in perfusion to the area under stimulation by O3-AHT. With repeated treatment, sufficient enough LOP may be generated to reach the bone marrow acting as repeated stressors to simulate erythrogenesis and the upregulation of antioxidant enzyme upregulation. O3 also causes a reduction in nicotinamide adenine dinucleotide (NADH) and assists in the oxidation of cytochrome c.,

O3 has also been shown to improve blood circulation and oxygen delivery to ischemic tissues. Multiple studies have provided evidence that the correction of chronic oxidative stress via the increase of antioxidant enzymes in O3 can increase erythroblast differentiation. This leads to a progressive increase in erythrocytes and preconditions them to having resilience towards oxidative stress. This is known as “oxidative preconditioning”., Also, O3 increases levels of prostacyclin, a known vasodilator.

Additionally, it was speculated that O3's oxidative capabilities would interfere with the endothelial production of NO and thus hinder vasodilation. However, studies have provided evidence that because NO is not substantially transported in the vasculature of the blood, a deleterious interaction is unlikely. Since HO-derived bilirubin31 has been demonstrated to interact with NO,, O3-induced HO upregulation could modify NO production and alter vasodilation.

Unpredictably, studies have shown an increase of NO, which led to speculation of O3's ability to activate genes associated with NO synthase expression to further promote higher levels of NO formation. Moreover, O3's stimulation of antioxidant enzymes are also speculated to increase NO levels. While endothelial generation of superoxide disrupts the activity of NO, O3 upregulates the enzymes to ameliorate the downstream effects of ROS responsible for deleterious vasoconstriction.,

The prophylactic role of O3 has been explored with hepatic ischemia/reperfusion (I/R) injury, a phenomenon associated with liver transplantation. Hepatic I/R is a clinically unsolved problem mainly due to the unknown mechanisms that are the foundations of this ailment. In summary, O3 oxidative preconditionings (ozoneOPs) were found to protect against liver I/R injury through mechanisms that promote a regulation of endogenous NO concentrations and the maintenance of an adequate cellular redox balance. OzoneOPs are postulated to upregulate endogenous antioxidant systems and generate an increase in NO molecule generation, both of which are protective orders against liver and pancreas damage. The results in this animal model provided evidence that ozoneOPs protected against liver I/R via an increase in concentrations of endogenous NO and prime cells to have a more balanced redox system. Additionally, enhanced activation of adenosine A1 receptors in rat models have been observed with ozoneOPs in liver I/R.

Further studies have expanded upon this postulation by applying O3 therapy to renal I/R in rats. Renal I/R is a primary cause of acute renal failure after transplantation surgery. The findings of a study by Orakdogen et al. indicated that the ozoneOPs allowed for a protective element when facing I/R. Following an increase in endothelial NO synthase and inducible NO synthase expression, it was concluded that ozoneOPs were intimately related to the increasing NO production as well as reducing renal damage by suppressing endothelin 1.

Cerebral vasospasm after subarachnoid hemorrhage is a significant detriment to the recovery of patients. An animal model examined the effects intravenous O3 therapy on vasospasms in the rat femoral artery. Histopathological and morphometric measurements provided evidence that O3 therapy decreased morphometric changes, disruption of endothelial cells, and hemorrhages that are a result of vasospasm. The study speculated the anti-oxidative and anti-inflammatory effects of O3 might be a prudent treatment for posthemorrhagic vasospasm.

Pathogen inactivation

When bacteria are exposed to O3 in vitro, the phospholipids, and lipoproteins that are within the bacterial cell envelope are oxidized. As this occurs, the stability of the bacterial cell envelope is attenuated. Moreover, evidence has demonstrated O3 to interact with fungal cell walls like bacteria. This disrupts the integrity of the cytosolic membrane and infiltrates the microorganisms to oxidize glycoproteins, glycolipids, and block enzymatic function. The combination of these reactions causes inhibition of fungi growth and mortality of bacteria and fungi.,, In vitro, O3 has been shown to interfere with virus-to-cell contact in lipid-enveloped viruses via oxidation of lipoproteins, proteins, and glycoproteins, thus interfering with the viral reproductive cycles.,,

Specifically, animal models have shown that O3 therapy as an adjunct to vancomycin enhances the animal's capability to eliminate methicillin-resistant Staphylococcus aureus mediastinitis.

Immune system activation

In vivo, O3 therapy has been shown to have multifaceted effects when interacting with PUFA. As stated previously, O3 reacts with PUFA and other antioxidants, H2O2 and varies peroxidation compounds are formed. H2O2 readily diffuses into immune cells has been shown to act as a regulatory step in signal transduction and facilitating a myriad of immune responses., Specifically, increases in interferon, tumor necrosis factor, and interleukin (IL)-2 are seen. The increases with IL-2 are known to initiate immune response mechanisms. Additionally, H2O2 activates nuclear factor-kappa B (NF-κB) and transforming growth factor beta (TGF-β), which increase immunoactive cytokine release and upregulate tissue remodeling. H2O2 mediates the action of NF-κB by enhancing the activity of tyrosine kinases that will phosphorylate IκB, a subunit of the transcription factor NF-κB., Low doses of O3 have been shown to inhibit prostaglandin synthesis, release bradykinin, and increase secretions of macrophages and leukocytes. Having the correct amount of either of these oxidative markers can be used to create a sufficient rise in H2O2 and NO levels to stimulate the most notable increase in IL-8. IL-8 also activates NF-κB, allowing production of ROS scavengers.

Animal models using O3 have shown to reduce and prevent inflammatory responses steming from the presence of E. coli in the renal system., Additional studies have provided evidence of the anti-inflammatory effects of O3. A study by Chang et al. purified rheumatoid arthritis synovial fibroblast cells from human patients and injected them into immunocompromised mouse joints. Using an Ozonsan-α generator to deliver precise gas flows to vessels in the localized area, the authors discovered that 3% and 5% O3 application significantly decreased the proinflammatory cytokines IL-1β, IL-6, and TNF-α without any toxicity or severe side effects.

Studies have shown that human cancer cells from lung, breast, and uterine tumors are inhibited in a dose-dependent manner by O3 therapy in vitro. O3 concentrations of 0.3 and 0.5 ppm inhibited cancer cell growth by 40% and 60%, respectively. Furthermore, the noncancerous cell controls were not affected by these levels of O3. At 0.8 ppm, cancer cell growth was inhibited by more than 90%. However, the control cell growth was less than 50%. Additionally, as control cells aged, they exhibited further growth inhibition and morphological changes. The study speculated that as the healthy cells matured, there was a decrease in growth due to the increased cellular damage incurred by each division.

Clinical Utility

With its ever-growing ubiquity, O3 therapy is finding a place in many branches of medicine and medical specialties. In fact, its clinical use can be arranged systematically into cardiovascular (Additional Table 1), subcutaneous tissue (Additional Table 2), peripheral vascular disease (Additional Table 3), neurological (Additional Table 4), head and neck (Additional Table 5), orthopedic (Additional Table 6), gastrointestinal (Additional Table 7), and genitourinary (Additional Table 8). These indications are a product of human clinical trials conducted for specific pathologies related to the aforementioned systems. Despite a lack of direct support of O3 therapy, the current Food and Drug Administration regulations do not restrict the use of it in situations where it has proven its safety and effectiveness. Nonetheless, there has been support for its safety and effectiveness in multi-international studies.

Additional Table 1

Cardiovascular indications for O3 therapy

Additional Table 2

Subcutaneous tissue indications for O3 therapy

Additional Table 3

Peripheral vascular disease indications for O3 therapy

Additional Table 4

Neurological indications for O3 therapy

Additional Table 5

Head and neck indications for O3 therapy

Additional Table 6

Orthopedic indications for O3 therapy

Additional Table 7

Gastrointestinal indications for O3 therapy

Additional Table 8

Genitourinary indications for O3 therapy

Conclusions

O3 therapy can alter the natural history of several disease and disorders, with potentially many more yet untested. A plethora of laboratory studies have provided evidence of O3's antioxidant capabilities, as well as vascular, hematological, and immune system modulations. This evidence has been further substantiated in clinical trials with O3 therapy being useful in the cardiovascular, subcutaneous tissue, peripheral vascular disease, neurological, head and neck, orthopedic, gastrointestinal, and genitourinary pathologies. O3 therapy has proven especially beneficial in the diabetic foot, ischemic wounds, and peripheral vascular disease, areas in which O3 use is most prevalent. Upcoming laboratory and translational research should begin to develop protocols for O3-AHT in attempts to establish a dose-response relationship as it has demonstrated high utility in a myriad of pathologies at varying concentrations. Despite the presently compelling evidence, future studies should include more double-blind, randomized clinical trials with greater sample sizes, determination of longevity in benefits produced, as well as methods of measurements and analysis.

Acknowledgments

The authors are thankful to Drs. Kelly Warren, Inefta Reid, Todd Miller, and Peter Brink (Department of Physiology and Biophysics, Stony Brook University School of Medicine, Stony Brook, NY, USA) for departmental support, as well as Mrs. Wendy Isser and Ms. Grace Garey (Northport VA Medical Center Library, Northport, NY, USA) for literature retrieval.

Footnotes

Conflicts of interest

The authors have no conflicts of interest to declare.

 

Plagiarism check

Checked twice by iThenticate.

 

Peer review

Externally peer reviewed.

 

Open peer reviewers

Ozan Akca, University of Louisville, USA; Nemoto Edwin, University of New Mexico Health Sciences Center, USA; Mancuso Cesare, Università Cattolica del Sacro Cuore, Italy.

 

Additional files

Additional Table 1: Cardiovascular indications for O3 therapy.

Additional Table 2: Subcutaneous tissue indications for O3 therapy.

Additional Table 3: Peripheral vascular disease indications for O3 therapy.

Additional Table 4: Neurological indications for O3 therapy.

Additional Table 5: Head and neck indications for O3 therapy.

Additional Table 6: Orthopedic indications for O3 therapy.

Additional Table 7: Gastrointestinal indications for O3 therapy.

Additional Table 8: Genitourinary indications for O3 therapy.

 

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Journal article Open Access

Medical ozone modifies D-dimer, interleukin-6, lactic acid and oxidative stress levels: A possibility for the comprehensive treatment of COVID-19

 Ruíz-García, María Gema De la Cruz-Enríquez, Joel Rojas-Morales, Emmanuel Martínez-Vásquez, Aldrín Tobón-Velasco, Julio César Vázquez-Reyes, Christian Javier Jiménez-Ortega, José Carlos

ABSTRACT

Background: SARS-CoV-2-induced inflammation in COVID-19 is mediated by cytotoxic and pro-oxidant effects that potentiate alveolar, endothelial and immune tissue damage. Objective: We investigated the effect of medicinal ozone administration on the oxidative stress markers; in addition to D-dimer, lactic acid and interleukin-6 as markers of endothelial injury and inflammation process. Methodology: Medicinal ozone with oligo metals was administered in vivo (major autohemotherapy) and in vitro (peripheral blood), to subsequently determine the levels of: H2O2, NO, GPx, CAT, TAP, TBARs, D-dimer, lactic acid and interleukin-6. Results: Medicinal ozone administration with oligo metals induced changes in oxidative stress markers both in vitro and in vivo. The H2Oand TBARs levels decreased, in turn, NO levels increased (cardiovascular function marker). On the other hand, the levels of the antioxidant enzymes (GPx and CAT) show slightly increase, which indicates an antioxidant enzyme system regulation that counteracts the pro-oxidative effect of the infection. Furthermore, interleukin-6 levels decreased indicating the regulation of the systemic inflammatory process. Finally, lactic acid and D-dimer levels were decreased, establishing an improvement of energy metabolism and endothelial function respectively. Conclusion: The medicinal ozone administration induce decrease in the markers levels of oxidative stress, inflammation and cellular damage, improving the enzymatic antioxidant capacity and cellular metabolism with decrease plaque aggregation that contribute to reducing the risk of vascular endothelial damage. These benefits could be feasible to integrate in the treatment of endothelial injury in COVID-19 patients.

 

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