The effects of using nitric oxide (NO) donors and inhibitors in experimental strongyloidiasis were showed using, both naïve and dexamethasone immunosuppressed BALB/c mice infected with Strongyloides venezuelensis. Aminoguanidine, an inhibitor of inducible NO synthase and LA419 a NO donor, were administered. Dexamethasone was used to induce immunosuppression. The study in BALB/c mice revealed increases in counts of fecal eggs, larvae in lungs and parasitic females following treatment with aminoguanidine, while mice treated with LA419 had limited egg output with low larval and adult recoveries. Mice immunosuppressed with dexamethasone developed hyperinfection with high long lasting fecal egg emission, high numbers of larvae in lungs and high numbers of parasitic females in the intestine even when the infection had already been cleared in non-immunosuppressed infected controls. Mice treated with dexamethasone and aminoguanidine had the highest egg output and the highest larva and parasitic female recovery showing a severe hyperinfection syndrome. In contrast, treatment with dexamenthasone and LA419 resulted in a controlled hyperinfection syndrome and these mice were able to eliminate the parasite. Therefore, NO modulation appears to be a determinant factor in severe strongyloidiasis and further studies should be conducted to confirm in other experimental models.

2011-11-01·Arteriosclerosis, Thrombosis, and Vascular Biology1区 · 医学

Coordinated Inhibition of Signaling (Phosphatidylinositol 3-Kinase-γ, 14-3-3ζ, and Growth Factor Receptor–Bound Protein 2) and Cytoskeleton Protein Translocation

1区 · 医学

Article

作者: Vilahur, Gemma ; Peña, Esther ; Molins, Blanca ; Badimon, Lina ; Padro, Teresa

Objective—Growing insight into the antiplatelet properties of new nitric oxide (NO) donors has expanded their potential use in cardiovascular diseases. As such, we reported that oral administration of a new exogenous NO donor (LA419) induced significant inhibition of platelet deposition on damaged vascular wall without provoking hypotension in an in vivo experimental model. Thrombin is one of the major triggers of platelet deposition and thrombosis on injured vessels; however, the effects of NO on thrombin-induced platelet activation are not fully known. Here, our aim was to investigate the inhibitory effects of exogenous NO administration on the major changes in platelet proteins induced by thrombin.Methods and Results— Platelets were obtained from a group of swine orally treated with LA419 (0.9 mg kg −1 ) or placebo for 8 days. Washed platelets were incubated with thrombin (0.4 NIH U/mL). Platelet proteins were then sequentially extracted based on differential solubility and studied by two-dimensional electrophoresis, mass spectrometry (matrix-assisted laser desorption ionization/time of flight), Western blot, and confocal immunofluorescence. NO treatment abrogated thrombin effects on 24 proteins involved in actin assembly, signaling, and metabolic activity. NO treatment prevented thrombin-induced translocation of gelsolin, filamin, 14-3-3ζ, phosphatidylinositol 3-kinase-γ isoform, and growth factor receptor-bound protein 2 (Grb2). Conclusion—Our results show that exogenous NO donor treatment renders platelets less sensitive to thrombin activation and inhibits thrombosis by interfering with the platelet shape change machinery.

2011-01-01·Proceedings of the Western Pharmacology Society

Treatment with LA-419 prevents monocrotaline-induced pulmonary hypertension and lung injury in the rat.

Article

作者: Martin, M T ; Giménez, F ; Mourelle, M

We evaluated the therapeutic potential of LA-419, a hybrid organic nitrate that donates nitric oxide and thiol groups, to improve pulmonary arterial hypertension in an experimental model induced by monocrotaline in the rat. Treatment with LA-419 from the first day after monocrotaline administration prevented the increase in pulmonary pressure as well as the increases in ventricle/body weight and pulmonary artery wall thickness. Administration of LA-419 after establishment of hypertensive status also resulted in an improvement of these parameters. Both preventive and therapeutic treatments reduced mortality. The antioxidant effect of LA-419 was comparable to that achieved with a-tocopherol. Pulmonary remodeling accomplished by LA-419 could be attributed to a balanced antioxidant effect associated with its nitric oxide/SH donor capability. Thus, LA-419 might represent a new therapeutic approach in severe pulmonary hypertension in humans.

100 项与 LA-419 相关的药物交易

登录后查看更多信息