ABSTRACT
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10%O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration),the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.
Subject(s)
Hypertension, Pulmonary , Rats , Male , Animals , Hypertension, Pulmonary/drug therapy , Simvastatin/pharmacology , Simvastatin/therapeutic use , Dehydroepiandrosterone Sulfate , Pulmonary Artery , Hypoxia/complications , Hypoxia/drug therapy , Hypoxia/pathology , Dehydroepiandrosterone/pharmacology , Dehydroepiandrosterone/therapeutic useABSTRACT
An effect of cyclosporin A on lipid peroxidation in isolated rat hepatocytes was tested. A significant increase in lipid peroxidation marker (the concentration of lipofuscin-like pigments) was observed in samples incubated with cyclosporin A in comparison with the control. When hepatoprotective flavonoid silybin was added, the production of lipofuscin-like pigments decreased significantly. This result indicates a potential positive role of silybin in lowering of cyclosporin A side effects associated with the production of reactive oxygen species and plasma membrane damage.
Subject(s)
Cyclosporine/pharmacology , Hepatocytes/drug effects , Lipid Peroxidation/drug effects , Animals , Antioxidants/pharmacology , Cells, Cultured , Hepatocytes/cytology , Hepatocytes/metabolism , Male , Membrane Lipids/metabolism , Molecular Structure , Oxidation-Reduction/drug effects , Rats , Rats, Wistar , Silybin , Silymarin/chemistry , Silymarin/pharmacology , Time FactorsABSTRACT
Transgenic plants with genetically increased or decreased levels of cytokinins were used to investigate the effect of cytokinin level on the production of ethylene, a plant hormone with suggested role in senescence, and the production of nitric oxide, potentially important signalling and regulatory molecule. The production of these gases was followed during the course of leaf development and senescence. The production of ethylene and nitric oxide is under genetic control of genes other than those involved in regulation of senescence. The difference in basic ethylene and NO levels in different tobacco cultivars was higher than their changes in senescence. The results of this study did not indicate a direct link between ethylene production and cytokinin levels. However, there was a decreased production of NO in senescent leaves. Low cytokinins level was associated with increased NO production during leaf development. Protein nitrotyrosine proved to be a better indicator of the reactive nitrogen species than measuring of the NO production. Higher nitrotyrosine concentrations were found in insoluble proteins than in the soluble ones, pointing to membrane proteins as the primary targets of the reactive nitrogen species. In plants with elevated cytokinin levels the content of nitrated proteins decreased both in soluble and insoluble fractions. This finding indicates an antioxidative function of cytokinins against reactive nitrogen species.
Subject(s)
Cytokinins/physiology , Ethylenes/biosynthesis , Nicotiana/metabolism , Nitric Oxide/biosynthesis , Plant Leaves/metabolism , Tyrosine/analogs & derivatives , Cytokinins/metabolism , Gene Expression Regulation, Plant , Plant Growth Regulators/metabolism , Plant Growth Regulators/physiology , Plant Leaves/genetics , Plant Leaves/physiology , Plants, Genetically Modified , Nicotiana/genetics , Nicotiana/physiology , Tyrosine/biosynthesisABSTRACT
Many chronic inflammatory pulmonary diseases are associated with inflammation and oxidative stress. A complex interplay between the specific cause of the diseases, the type and intensity of inflammation and oxidative stress, results in the clinical picture and reveals the probability of progression of the specific disease. The presence of inflammation and oxidative stress has been established in interstitial lung diseases, cystic fibrosis, bronchiectasis, adult respiratory distress syndrome, chronic obstructive lung diseases and asthma. Noninvasively obtained markers of inflammation and oxidative stress from the breath may assist in diagnosis of pulmonary diseases, assessment of diseases severity and response to treatment. Exhaled markers include NO, CO, H2O2, ethane, pentane, and isoprostanes.
