Silvia Menéndez

Effects of ozone oxidative preconditioning on nitric oxide generation and cellular redox balance in a rat model of hepatic ischaemia-reperfusion.

Background: Many studies indicate that oxygen free‐radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species and protecting against liver ischaemia–reperfusion (I/R) injury.

Ozone oxidative preconditioning is mediated by A1 adenosine receptors in a rat model of liver ischemia/ reperfusion.

The liver is damaged by sustained ischemia in liver transplantation, and the reperfusion after ischemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the role of A1 adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R. By using a specific agonist and antagonist of the A1 subtype receptor (2‐chloro N6 cyclopentyladenosine, CCPA and 8‐cyclopentyl‐1,3‐dipropylxanthine, DPCPX respectively), we studied the role of A1 receptor in the protective effects of OzoneOP on the liver damage, nitiric oxide (NO) generation, adenosine deaminase activity and preservation of the cellular redox balance. Immunohistochemical analysis of nuclear factor‐kappa B (NF‐κB), tumor necrosis factor alpha (TNF‐α) and heat shock protein‐70 (HSP‐70) was performed. OzoneOP prevented and/or ameliorated ischemic damage. CCPA showed a similar effect to OzoneOP + I/R group. A1AR antagonist DPCPX blocked the protective effect of OzoneOP. OzoneOP largely reduced the intensity of the p65 expression, diminished TNF‐α production, and promoted a reduction in HSP‐70 immunoreactivity. In summary, OzoneOP exerted protective effects against liver I/R injury through activation of A1 adenosine receptors (A1AR). Adenosine and .NO produced by OzoneOP may play a role in the pathways of cellular signalling which promote preservation of the cellular redox balance, mitochondrial function, glutathione pools as well as the regulation of NF‐κB and HSP‐70.

Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats.

Rheumatoid Arthritis (RA) is the most prevalent chronic condition present in ~1% of the adult population. Many pro-inflammatory mediators are increased in RA, including Reactive Oxygen Species such as nitric oxide NO, pro-inflammatory cytokines as tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and other molecules. Ozone oxidative postconditioning has regulatory effects on some pathological targets associated with RA. Thus, the aim of this study was to investigate the efficacy of ozone therapy in PG/PS-induced arthritis in rats in point of joints inflammation and morphology. Moreover, cytokines, nitric oxide and oxidative stress levels in spleen homogenates were evaluated. Ozone treatment ameliorated joint damage, reduced TNF-α concentrations as well as TNF-α and IL-1β mRNA levels. Besides, cellular redox balance, nitric oxide and fructolysine levels were reestablished after ozone oxidative postconditioning. It was concluded that pleiotropic ozones effects clarify its therapeutic efficacy in RA. Decreasing inflammation and joint injury, reduction of pro-inflammatory cytokines, TNF-α and IL-1β transcripts and re-establishment of cellular redox balance after ozone treatment were demonstrated.

Ozone Therapy in Patients with Retinitis Pigmentosa

The aim of this study is to determine the efficacy of ozone therapy in patients with Retinitis Pigmentosa (RP). A controlled, randomized, double blind clinical trial involving 68 patients was performed. Patients were divided into 2 groups: ozone, patients treated with ozone by rectal administration (dose=10 mg), during 15 sessions; control, as ozone group, but using oxygen. The main outcome variable was the visual field area (VFA). Results demonstrated a significant improvement (SI) in 88.2% of patients treated with ozone in comparison with 23.5% achieved in the control group. In the ozone group, VFA tend to stabilize beyond a mean time of 6.83 months with a loose in SI afterward. A temporal positive effect of ozone therapy. Over the natural course of RP, was found.

Ischemic and Ozone Oxidative Preconditioning in the Protection Against Hepatic Ischemic-Reperfusion Injury

It has been demonstrated that ozone, probably through a mechanism of oxidative preconditioning (OP), protected the liver against the damage mediated by reactive oxygen species. Taking into account that iscehmic preconditioning (IschP) is also a protective mechanism, a comparative study between both preconditioning settings was performed in order to study the effectiveness of both protective procedures. Rats were randomly divided into 4 groups: 1- control, sham operated (anesthesia and laparotomy plus surgical manipulation); 2- I/R (ischemia for 90 min followed by 90 min reperfusion); 3- Ischp+I/R, as group 2 but submitted to a previous ischemic preconditioning (ischemia 10 min and reperfusion 10 min); 4- OzoneOP+I/R, as group 2 but submitted to a pervious oxidative preconditioning with 15 sessions, daily, of ozone by rectal administration (dose of 1 mg/kg). The comparison between both preconditionings showed no biochemical differences for the parameters evaluated. Nevertheless, the histological study demonstrated that the protective effect produced by the OzoneOP is superior to that achieved with the IschP.

Application of Ozone Therapy in Patients with Knee Osteoarthritis

Osteoarthritis is a common degenerative joint disease. Taking into account the ozone (O3) effects in cellular redox balance and upon biomarkers of inflammation, the aim of this study was to evaluate the action of ozone therapy in oxidative stress parameters in synovial fluid of patients suffering of knee osteoarthritis and their clinical evolution. In 42 patients, O3 was administered rectally and by intra-articular applications. Synovial fluid was extracted for the measurement of parameters associated with oxidative stress. Also, evaluation of the joint capacity, pain, and ultrasound imaging were performed. Combined ozone therapy produced an intra-articular redox balance and a significant reduction of pain.

Ozone Biological Response in Kidneys of Rats Submitted to Warm Ischemia

A biochemical and morphofunctional renal study, applying different sessions of rectal ozone (O3) before a warm ischemia, was performed. Rats were divided in: 1-control, a medial abdominal incision was performed for the exposure of the kidneys; 2-ischemia, animals with a bilateral renal ischemia (30 min), with subsequent reperfusion (3 h); groups 3, 4 and 5 – (O3+ischemia), as group 2, but with previously treatment of 5, 10 and 15 sessions of rectal ozone, respectively; groups 6, 7 and 8 – (O2+ischemia), as groups 3, 4 and 5, respectively, but using rectal oxygen. A significant decrease of the flow and renal filtration, with high values of fructosamine and phospholipase A2, in the ischemia and oxygen groups, with respect to control and ozone groups was obtained without any statistical difference among them. Morphological alterations were significantly less in the groups pretreated with ozone, with better results for 10 and 15 sessions.

Ozone Therapy in Retinitis Pigmentosa Patients: Clinical Evolution and Oxidative Stress Behavior in Retinitis Pigmentosa Patients Treated with Ozone Therapy over 20 Years

Retinitis pigmentosa is characterized by bad night vision, decrease of visual field and/or acuity. The aim of this article is to assess ozone therapys efficacy in these patients, treated twice a year over 20 years. Forty patients received ozone via the rectal way, during 20 sessions as the only treatment, with repetition of this cycle every 6 months, and 16 received other medical treatments (control group). A significant decrease of the visual field in the control group in respect to the ozone group was observed after 20 years of treatment. In the ozone group, 50% of patients improved their visual field, accompanied with homeostasis in redox state. It is recommended to apply ozone therapy at 6-month intervals in order to maintain visual capabilities. The opinions and conclusions expressed in this article are those of the authors and contributors, and do not necessarily reflect those of the International Ozone Association, the editors, Editorial Board, or Taylor & Francis. Readers are to make their own decisions with regard to the work presented. These medical articles are enclosed, as in the past, as a service to the members of the IOA interested in medical applications.