Ozone protective effects against PTZ-induced generalized seizures are mediated by reestablishment of cellular redox balance and A1 adenosine receptors.

OBJECTIVES: Epilepsy is a common seizure disorder affecting approximately 70 million people worldwide. Mitochondrial dysfunction and antioxidant/prooxidant imbalance are emerging as factors that contribute to epileptogenesis. As medical ozone was able to reestablish cellular redox balance and to maintain the protective effects mediated by A1 receptors (A1Rs), the aim of this work was to study ozone's effects on antioxidant/prooxidant balance and to clarify if A1Rs play a role in ozone's protective actions against pentylenetetrazole (PTZ)-induced convulsions in mice. METHODS: Influence of ozone's treatments in mice submitted to PTZ-induced seizures was studied. Ozone was administered by rectal insufflation 1 mg/kg (5, 10, 15, 20 treatments), one per day, of 1-1·5 ml at an ozone concentration of 20 µg/ml. Mice received PTZ (90 mg/kg i.p.) 24 hours after the last ozone treatment. Oxygen control groups 26 mg/kg were introduced. Latency to first seizure was determined. Antioxidant/prooxidant balance in brain homogenates was studied. A1 adenosine receptors' effects on ozone's protective actions against seizures were evaluated using 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). RESULTS: Highest latency was observed when mice received 15 ozone treatments. Oxygen + PTZ group did not achieve protection against neither convulsions nor brain oxidative injury. Fifteen treatments of ozone protected against biomolecules oxidative damage and the antioxidant systems as well. 8-Cyclopentyl-1,3-dipropylxanthine abolished the ozone's protection. CONCLUSIONS: Ozone therapy increased the latency for the first seizure and the survival percentage. These effects are discussed in point of ozone's capacity to reestablish cellular redox balance, decrease biomolecules damage, and regulate activation of A1 adenosine receptors in PTZ-induced seizures.

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-1ß) 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-1ß mRNA levels. Besides, cellular redox balance, nitric oxide and fructolysine levels were reestablished after ozone oxidative postconditioning. It was concluded that pleiotropic ozone's effects clarify its therapeutic efficacy in RA. Decreasing inflammation and joint injury, reduction of pro-inflammatory cytokines, TNF-α and IL-1ß transcripts and re-establishment of cellular redox balance after ozone treatment were demonstrated.

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 A(1) adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R. By using a specific agonist and antagonist of the A(1) subtype receptor (2-chloro N6 cyclopentyladenosine, CCPA and 8-cyclopentyl-1,3-dipropylxanthine, DPCPX respectively), we studied the role of A(1) 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-kappaB), tumor necrosis factor alpha (TNF-alpha) 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. A(1)AR antagonist DPCPX blocked the protective effect of OzoneOP. OzoneOP largely reduced the intensity of the p65 expression, diminished TNF-alpha production, and promoted a reduction in HSP-70 immunoreactivity. In summary, OzoneOP exerted protective effects against liver I/R injury through activation of A(1) adenosine receptors (A(1)AR). 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-kappaB and HSP-70.