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

Abstract

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.

Keywords:

• Adenosine
• Oxidative stress
• Ozone
• Seizures