Oxygen radical scavengers protect against eosinophil-induced injury in isolated perfused rat lungs.
ABSTRACT The protective effect of oxygen radical scavengers on lung injury induced by activated eosinophils was examined in isolated perfused rat lungs. Eosinophils were obtained by bronchoalveolar lavage from rats infected with Toxocara canis and activated with phorbol myristate acetate (PMA). There were no changes in pulmonary vascular (RT) and airway (Raw) resistances and only minimal changes in vascular permeability assessed using the capillary filtration coefficient (Kf,c) in PMA control lungs and nonactivated eosinophil-treated lungs. In lungs receiving 3 x 10(6) PMA-activated eosinophils, there were significant increases from baseline of 7.3-fold in RT at 30 min, primarily due to the constriction of small arteries and veins; 3.6-fold in Kf,c at 90 and 130 min; and 2.5-fold in Raw. The lungs also became markedly edematous. Both superoxide dismutase and catalase pretreatment prevented the significant increase in Kf,c and lung wet-to-dry weight ratios and partially attenuated the increase in Raw, but did not significantly inhibit the increase in RT induced by activated eosinophils. Heat-inactivated catalase did not attenuate the eosinophil-induced increases in Kf,c, Raw, or RT. Thus, activated eosinophils acutely increased microvascular permeability primarily through production of oxygen free radicals. The free radical scavengers superoxide dismutase and catalase partially attenuated the bronchoconstriction but had no significant effect on the vasoconstriction induced by activated eosinophils.
- SourceAvailable from: Jose Luis Perez Arellano[Show abstract] [Hide abstract]
ABSTRACT: The direct effect of nitric oxide (NO) on the viability of Toxocara canis larvae was studied. We observed that the nitric oxide donors, SIN-1 and SNOG, exert no cytotoxic effect on the in vitro viability of T. canis larvae. In addition, we developed a model in rats to elucidate the role of NO during T. canis infection. We evaluated different indicators in four experimental groups: morphological parameters, the total number cells and cell types recovered, nitrite and protein concentration, lactate dehydrogenase and alkaline phosphatase enzymatic activity in the bronchoalveolar lavage fluid, lung index and detection of anti-T. canis specific antibodies. We observed significant differences between non-infected and infected groups. The infected animals treated with the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine were less damaged than infected, non-treated animals. Our results suggest that the in vivo inhibition of the synthesis of NO triggered by iNOS diminishes the deleterious effects of the parasite upon the host, especially the vascular alterations in the lungs. We could show that in vivo production of NO induced by infection with T. canis results in direct host damage. Thus, this induction may constitute an evasion/adaptation mechanism of the parasite.Parasite Immunology 11/2002; 24(11-12):511-20. DOI:10.1046/j.1365-3024.2002.00598.x · 1.85 Impact Factor
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ABSTRACT: The effect of oral and intraperitoneal supply of sodium selenite on the immune response to, and the course of T. canis larvae infection in mice were determined. The number of worms in the host tissue was reduced but the migratory route of larvae was not affected. Selenite (Se) supplementation influences Se retention in the liver, enhanced IL-5 and eosinophil responses and evoked IL-6 production in mice infected with T. canis. The enhanced protection in mice given Se intraperitoneally was associated with high levels of parasite-specific IgE, and enhanced concentration of Th1-related cytokines such IL-12p70, TNF-α and IFN-γ. In mice given Se orally, the predominant cytokines produced were IL-10, MCP-1 and IL-6 and these mice had lower protection. In conclusion, Se supplementation increases production of specific cytokines in mice infected with T. canis and increases protection against infection.Parasite Immunology 06/2008; 30(8):394-402. DOI:10.1111/j.1365-3024.2008.01039.x · 1.85 Impact Factor
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ABSTRACT: Correlation between the level of reactive oxygen species (ROS) generated by airway inflammatory cells and superoxide dismutase (SOD) activity of pulmonary tissue during an asthma attach was investigated in a guinea pig model of allergic asthma. In addition, the influence of SOD inhibition by diethyldithiocarbamate (DDC, Cu-chelating agent) on the airway was investigated in terms of pulmonary function during an asthma attach. Relative to controls, the capacity of bronchoalveolar lavage fluid (BAL) cells to release ROS was significantly increased in guinea pigs sensitized with ovalbumin (OA) as the antigen, and significantly increased in guinea pigs with an asthma attack provoked by the inhalation of OA. SOD activity was increased significantly in the antigen-sensitized group. The asthma provocation group showed a tendency for increase in total SOD activity, compared with the sensitization group, whose increase was dependent on the increase in copper, zinc-SOD (Cu, Zn-SOD) activity. Pretreatment with DDC increased the severity and duration of the asthma attack. These results were indicated that Cu, Zn-SOD was closely involved in the asthma process, particularly in the scavenging of oxygen radicals secreted from BAL cells.Free Radical Research 07/2002; 36(6):601-6. DOI:10.1080/10715760210872 · 2.99 Impact Factor