Ricardo González Álvarez

Preconditioning with ozone/oxygen mixture induces reversion of some indicators of oxidative stress and prevents organic damage in rats with fecal peritonitis

Objective and designReactive oxygen and nitrogen species are involved in the pathogenesis of sepsis syndrome with peritonitis and the septic shock. The aim of this study was to determine whether ozone oxidative preconditioning (OOP) may exert beneficial effects in the prevention and treatment of sepsis syndrome in rats inoculated by the intraperitoneal route (i.p.) with fecal material and also to determine if antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) may exert protective effects against this systemic inflammatory disorder.Materials and methodsMale Wistar rats were used. SOD and GPx activities were determined in erythrocytes. Thiobarbituric acid reactive substances (TBARS) content as biomarkers of oxidative stress, alanine amino transferase (ALT), aspartate amino transferase (AST) and creatinine (CRE) were measured in blood serum and myeloperoxidase (MPO) in lung tissue as markers of organs damage.ResultsIn rats submitted to OOP, SOD and GPx activities were significantly increased and it was accompanied by significant decrease of TBARS content in blood serum. OOP also significantly reduced levels of ALT, AST and CRE in blood serum as well as MPO in rat lung.ConclusionThe results support the important role of SOD and GPx in the protective effects of OOP against organ damage induced by fecal peritonitis in rats.

A protective action of disodium cromoglycate against the contraction of guinea-pig ileum induced by various pharmacological stimulants

The effect of disodium cromoglycate (DSCG) on the contraction of isolated guinea-pig ileum induced by histamine, acetylcholine and serotonin has been investigated. DSCG protected ileum against all agents tested. The action of DSCG at concentrations of 10−3 to 10−2M was both dose- and time-dependent. Furthermore, DSCG inhibited compound 48/80-induced histamine release from isolated mast cells over the same range of concentrations.The anti-histaminic action of DSCG was reversible and after 2 h the ileum responded normally to histamine.DSCG-induced inhibition of the contractile response to histamine could be overcome by increasing concentrations of histamine but not by extracellular calcium.A mechanism of the action of DSCG, either against the contraction of ileal smooth muscle or against histamine release from mast cells, is discussed with a view to the inhibition of the utilization of calcium ions by both cells.

New light on the mechanism of action of disodium cromoglycate.

Disodium cromoglycate (DSCG) shows a prolonged protective effect against histamine on the smooth muscle of guinea pig ileum. Preventing allergen-induced mediator release from mast cells as well as protection of smooth muscle against mediators already released can both explain a beneficial effect of DSCG in the treatment of bronchial asthma and food allergy. It is believed that disappointing clinical trials with many new anti-allergic drugs, e.g. RS 7540, can be explained by the lack of a protective effect on the smooth muscle of target organs.

Ascorbic acid and pyridoxine in experimental anaphylaxis.

Two vitamins, ascorbic acid (AA) and pyridoxine have been suggested by others as useful drugs for the treatment of bronchial asthma, although the views concerning AA are controversial. We have tested both vitamins in some models of histamine release and experimental anaphylaxis. AA does not inhibit mast cell degranulation induced by phospholipase A and histamine release from isolated rat mast cells induced by compound 48/80 or antigen (egg albumin). On the contrary, in the latter tests pyridoxine exerts inhibition in a range of concentrations from 10−3−10−2 M. We conclude: 1. There is no experimental basis for considering ascorbic acid as a prophylactic antiasthmatic drug as is disodium cromoglycate. 2. Pyridoxine must receive additional basic and clinical investigations in this field.Two vitamins, ascorbic acid (AA) and pyridoxine have been suggested by others as useful drugs for the treatment of bronchial asthma, although the views concerning AA are controversial. We have tested both vitamins in some models of histamine release and experimental anaphylaxis. AA does not inhibit mast cell degranulation induced by phospholipase A and histamine release from isolated rat mast cells induced by compound 48/80 or antigen (egg albumin). On the contrary, in the latter tests pyridoxine exerts inhibition in a range of concentrations from 10−3−10−2M.We conclude: 1. There is no experimental basis for considering ascorbic acid as a prophylactic antiasthmatic drug as is disodium cromoglycate. 2. Pyridoxine must receive additional basic and clinical investigations in this field.

Protective Effects of Ketotifen on Guinea Pig Trachea

We have studied the effects of ketotifen (Ke), an effective antiallergic drug, on guinea pig trachea. Ke (10-6-5 × 10-5M) inhibits contractions induced in this preparation by acetylcholine, prostaglandin F2α barium chloride, potassium chloride and electrical stimulation. These results provide evidence for protective effects of Ke in airways. Furthermore, Ke exerts also a neural inhibitory effect on postganglionic parasympathetic fibers of guinea pig trachea. These findings resemble the effects reported previously for disodium cromoglycate by us and might be relevant for antiasthmatic and antiallergic properties of Ke.

Further studies on the effects of disodium cromoglycate on guinea pig ileum.

Transmural electrical stimulation was carried out on innervated strips of the longitudinal muscle of guinea pig ileum. Disodium cromoglycate (DSCG) inhibited the electrically induced contractions.Five minutes later, prostaglandin E2 (2.5 ng/ml) was added to the bath and it reversed the action of DSCG. Furthermore, DSCG inhibits significantly the guinea pig ileum contractions induced by nicotine and also those induced by histamine and acetylcholine on ileum denervated by cooling.These results suggest that DSCG effects on guinea pig ileum contraction are mediated by membrane-stabilizing properties of this drug on smooth muscle fibres as well as on myenteric plexus.

Effects of ozone oxidative preconditioning on different hepatic biomarkers of oxidative stress in endotoxic shock in mice

In endotoxic shock, variations are known to occur in different biochemical parameters of oxidative stress. Ozone oxidative preconditioning (OOP) is a good candidate to restore the redox balance on different tissue. This investigation examined the effect of OOP on different biomarkers of oxidative stress in hepatic tissue of mice treated with lipopolysaccharide (LPS). LPS doses of 30 mg/kg were administered intraperitoneally (i.p.) and pretreatment with ozone/oxygen mixture (OOM) was applied i.p. at 0.2, 0.4, and 1.2 mg/kg once daily during 5 days before LPS injection. The mice were euthanized under ether atmosphere at different times, 1 and 24 h after LPS injection. Hepatic tissue from all animals was taken for biochemical determinations of oxidative stress parameters such as thiobarbituric acid reactive substances (TBARS) content and activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST). The results demonstrated that OOP reduces levels of TBARS content and increases the activity of GPx in hepatic tissue. In conclusion, OOP was able to recover the redox balance and in this way to protect the animals against the oxidative damage induced by endotoxemia.