The rectal insufflation of a judicious dose of ozone, selected from that used in clinical practice, is able to promote oxidative preconditioning or oxidative stress tolerance preventing the hepatocellular damage mediated by free radicals. In order to evaluate the effects of ozone oxidative preconditioning on carbon tetrachloride‐mediated hepatotoxicity, the following experimental protocol was designed: group 1 (negative control, sunflower oil i.p.); group 2 (CCl4 in sunflower oil, 1 ml kg−1 i.p.); group 3 (15 ozone–oxygen pretreatments at a dose of 1 mg kg−1 via rectal insufflation + CCl4 as in group 2); group 4 (ozone control group, 15 ozone–oxygen pretreatments + sunflower oil i.p.). Ozone pretreatment prevented glycogen depletion (as demonstrated by biochemical and histopathological findings) and avoided lactate overproduction associated with the hepatotoxic effects of CCl4. The administration of CCl4 increased lipid peroxidation (as measured by thiobarbituric acid‐reactive substances) and uric acid levels and inhibited superoxide dismutase activity. All these deleterious effects induced by CCl4 were prevented by ozone pretreatment. The administration of ozone without CCl4 (ozone control group) did not produce any changes in the evaluated parameters. Our results showed that ozone treatment, in our experimental conditions, was able to prevent anaerobic glycolysis and oxidative stress induced by CCl4. Copyright © 2001 John Wiley & Sons, Ltd.

The effect of oral administration of Mangifera indica L. extract (QF808) on ischemia-reperfusion-induced neuronal death in the gerbil hippocampal CA1 sector was examined. Oral administration of QF808 for 7 days dose-dependently protected against neuronal cell death following transient ischaemia and reperfusion as assessed by histopathology. In addition, locomotor activity assessment prior to ischaemia and 7 days after correlated well with the histological results. To evaluate redox alterations by reactive oxygen species, total sulfhydryl, non-protein sulfhydryl groups (NPSH), malondialdehyde+4-hydroxyalkenals and total nitrogen oxide levels were assayed in hippocampus and cortex homogenates. QF808 treatment attenuated NPSH loss, nitrogen oxide levels and lipid peroxidation in the hippocampus. These results suggest that orally administered QF808 is absorbed across the blood-brain barrier and attenuates neuronal death of the hippocampal CA1 area after ischaemia-reperfusion. These protective effects are most likely due to the antioxidant activity of QF808.

Kainate induces a marked expression of cyclooxygenase-2 after its systemic administration. Because cyclooxygenase-2 activity is associated to the production of reactive oxygen species, we investigated the effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on kainate-induced in vivo oxidative damage in the rat hippocampus. A clinically relevant dose of nimesulide (6 mg/kg, i.p. ) was administered three times following kainate application (9 mg/kg, i.p.). After 24 h of kainate administration, the drastic decrease in hippocampal glutathione content and the significant increase in lipid peroxidation were attenuated in nimesulide-treated rats, suggesting that the induction of cyclooxygenase-2 is involved in kainate-mediated free radicals formation.

There is some anecdotal evidence that oxygen-ozone therapy may be beneficial in some human diseases. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. On the basis of preliminary data we postulated that controlled ozone administration would promote an oxidative preconditioning preventing the hepatocellular damage mediated by free radicals. Six groups of rats were classified as follows: (1) negative control, using intraperitoneal sunflower oil; (2) positive control using carbon tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone, pretreatment via rectal insufflation (15 sessions) and after it, CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen, as group 5, but using oxygen only. We have evaluated critical biochemical parameters such as levels of transaminase, cholinesterase, superoxide dismutase, catalase, phospholipase A, calcium dependent ATPase, reduced glutathione, glucose 6 phosphate dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4 administration, group 3 did not differ from group 1, while groups 2 and 4 showed significant differences from groups 1 and 3 and displayed hepatic damage. To our knowledge these are the first experimental results showing that repeated administration of ozone in atoxic doses is able to induce an adaptation to oxidative stress thus enabling the animals to maintain hepatocellular integrity after CCl4 poisoning.