Integrative Regulatory Therapy Research

Chapter 7: Oxidative Pre-conditioning Therapy

Ozone and UV Light

When most people hear the word ozone, they think of a protective layer of the atmosphere but aren’t really sure what it is beyond that. Ozone is oxygen but with the molecular structure O3 instead of O2. This additional molecule makes ozone a highly reactive oxidant. If inhaled, ozone can do some serious damage to our bodies. However, there is an application of this substance that is very therapeutic. But first, let's take a closer look at ozone.

In nature, ozone has a good side and a bad side. In the stratosphere, it acts as a shield, deflecting harmful UV irradiation. However, in the troposphere, ozone is a major component of the smog that harms humans, animals, and plants. When we breathe it, ozone can cause serious pulmonary and systemic side effects because it is such a powerful oxidant.

On the world scene, ozone therapy became an innovative medical approach in 1954, when Wehrly and Steinbart first described its application. They found that while the human respiratory tract reacts very negatively to ozone, human blood does not. In fact, when exposed to appropriate ozone concentrations, our blood tames the strong oxidant properties of ozone, thus eliminating any acute side effects. The benefits derived from this therapy are staggering.

The ozone autohemotherapy (O3-AHT) standard technique is to withdraw 150-200 ml of blood and expose it to an oxygen/ozone mixture at a specified ozone concentration, followed by intravenous reinfusion of this blood into the patient. Ozone rapidly decomposes in blood to generate reactive oxygen compounds that act as an oxidative stimulus to the body and interact immediately with several substances, namely fatty acids, cholesterol, proteins, and carbohydrates.

An important role of O3-AHT in the Oasis of Hope IRT protocols is to serve as a technique for "oxidative preconditioning" (1). Exposing cells to an acute and repeated mild oxidant stress typically leads to a compensatory increase in antioxidant defenses. This increase in tolerance to oxidative stress can be protective if a subsequent stronger oxidative stress is applied. Although the only cells exposed to oxidative stress during O3-AHT are the blood cells that are directly mixed with ozone (2) and reinfused, it seems likely that these cells will generate by-products of oxidant stress that other cells can "interpret" as signs of oxidative damage. This leads to induction of antioxidant defenses. In fact, several studies show that, when rats are pre-exposed to ozone (usually by rectal administration), they subsequently are protected from various oxidant stressors, including the chemotherapy drug cisplatin, the hepatotoxin carbon tetrachloride, the diabetes-inducing drug streptozotocin, endotoxin, and a brief cut-off of blood flow (ischemia-reperfusion) (3-8). In the study with cisplatin, it was intriguing that the ozone pretreatment did not influence that antioxidant status of the kidney in healthy rats. But, in rats treated with cisplatin, it prevented a decrease in kidney antioxidants (glutathione and antioxidant enzymes) seen in the rats given cisplatin without O3-AHT pretreatment; O3-AHT also maintained normal kidney function in the cisplatin-treated rats (3).

In addition to cisplatin, a number of chemotherapy agents are known to generate oxidant stress in the body. This stress can contribute to the damage to healthy tissues that can make chemotherapy a traumatic experience and limit the doses that can be used. For this reason, Oasis of Hope employs O3-AHT as an "oxidative preconditioning" strategy in an effort to limit the damaging impact of chemotherapy to healthy tissues such as the bone marrow, intestinal tract, kidney, and heart.

In addition to treating blood with ozone, we also expose it to ultraviolet light before reinfusing it into the patient. This is intended to boost the generation of oxidative stress and thereby improve the efficacy of oxidative preconditioning therapy. Without question, ozone therapy is rapidly becoming an essential tool for oncologists and an integral part of comprehensive treatment programs.