ABSTRACT
SCOPE: This study investigates the preventive effects of two pea (Pisum sativum) seed albumin extracts, either in the presence (pea seed extract [PSE]) or absence (albumin fraction from PSE [AF-PSE]) of soluble polysaccharides, in the dextran sodium sulfate (DSS) induced colitis in mice. METHODS AND RESULTS: Male C57BL/6J mice were assigned to five groups: one noncolitic and four colitic. Colitis was induced by incorporating DSS (3.5%) in the drinking water for 4 days, after which DSS was removed. Treated groups received orally PSE (15 g/kgâ day), or AF-PSE (1.5 g/kgâ day), or pure soy Bowman-Birk inhibitor (BBI; 50 mg/kgâ day), starting 2 wk before colitis induction, and maintained for 9 days after. All treated groups showed intestinal anti-inflammatory effect, evidenced by reduced microscopic histological damage in comparison with untreated colitic mice. The treatments ameliorated the colonic mRNA expression of different proinflammatory markers: cytokines, inducible enzymes, metalloproteinases, adhesion molecules, and toll-like receptors, as well as proteins involved in maintaining the epithelial barrier function. Furthermore, the administration of PSE, AF-PSE, or soy BBI restored bacterial counts, partially or totally, to values in healthy mice. CONCLUSION: PSE and AF-PSE ameliorated DSS-induced damage to mice, their effects being due, at least partially, to the presence of active BBI.
Subject(s)
Albumins/pharmacology , Anti-Inflammatory Agents/pharmacology , Colitis/drug therapy , Pisum sativum/chemistry , Seeds/chemistry , Animals , Cecum/drug effects , Cecum/microbiology , Colitis/chemically induced , Colon/metabolism , Colon/microbiology , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dextran Sulfate/adverse effects , Disease Models, Animal , Gastrointestinal Microbiome , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-12/genetics , Interleukin-12/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Intestinal Mucosa/metabolism , Intestines/drug effects , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
To date, the role that NO derived from endothelial NO synthase (eNOS) plays in the development of the injuries occurring under hypoxia/reoxygenation (H/R) in the lung remains unknown and thus constitutes the subject of the present work. A follow-up study was conducted in Wistar rats submitted to H/R (hypoxia for 30 min; reoxygenation of 0 h, 48 h and 5 days), with or without prior treatment using the eNOS inhibitor L-NIO (20 mg/kg). Lipid peroxidation, apoptosis, protein nitration and NO production (NOx) were analysed. The results showed that L-NIO administration lowered NOx levels in all the experimental groups. Contrarily, the lipid peroxidation level and the percentage of apoptotic cells rose, implying that eNOS-derived NO may have a protective effect against the injuries occurring during H/R in the lung. These findings could open the possibility of future studies to design new therapies for this type of hypoxia based on NO-pharmacology.
Subject(s)
Hypoxia/metabolism , Lung/metabolism , Nitric Oxide Synthase Type III/physiology , Nitric Oxide/physiology , Reperfusion Injury/prevention & control , Animals , Cytoprotection/drug effects , Enzyme Inhibitors/pharmacology , Hypoxia/complications , In Situ Nick-End Labeling , Lung/drug effects , Lung/pathology , Male , Nitric Oxide/metabolism , Nitric Oxide/pharmacology , Nitric Oxide Synthase Type III/antagonists & inhibitors , Nitric Oxide Synthase Type III/metabolism , Ornithine/analogs & derivatives , Ornithine/pharmacology , Oxygen/pharmacology , Rats , Rats, Wistar , Reperfusion Injury/etiology , Thiobarbituric Acid Reactive Substances/metabolism , Tyrosine/analogs & derivatives , Tyrosine/metabolismABSTRACT
Objetivo. Se lleva a cabo una revisión actualizada sobre las posibles causas celulares y moleculares que subyacen al proceso de envejecimiento cerebral así como a las enfermedades neurodegenerativas asociadas. Desarrollo. A partir de las lesiones morfológicas e histológicas que se detectan tanto en procesos neurodegenerativos como durante el envejecimiento fisiológico, se analizan las causas que conducen a la pérdida de neuronas y de conectividad nerviosa, así como a los procesos de reactividad glial, como base morfofuncional del deterioro de los procesos cognitivo e intelectual que caracterizan la senescencia. Se correlacionan todos estos datos con las posibles bases genéticas del proceso de envejecimiento, llevando a cabo una revisión de los hallazgos más relevantes sobre senescencia y muerte celular obtenidos en levaduras, mosca de la fruta y nematodos. Tras una breve revisión sobre gerontogenes y mecanismos de apoptosis, se analizan las causas inductoras del proceso de envejecimiento y neurodegeneración, y se interrelacionan las diferentes hipótesis que barajan las teorías más actuales sobre el tema. Finalmente se integran todos los datos celulares, bioquímicos y genéticos, a partir de la puesta en marcha de sistemas de transducción de señales que provocan la elevación de los niveles de calcio citosólico y el disparo del proceso de muerte celular. Conclusiones. Diversas causas inductoras, que pueden activar o inhibir grupos de genes, entre las que se cuentan, deficiencias de factores neurotróficos, hipoxia e hipoglucemia, excitotoxicidad, producción de radicales libres de oxígeno y de nitrógeno, desencadenan procesos de muerte neuronal responsables del envejecimiento y de las enfermedades neurodegenerativas asociadas (AU)
Subject(s)
Animals , Humans , Cell Death , Receptors, Glutamate , Apoptosis , Neurodegenerative Diseases , Oxidative Stress , Calcium , Aging , Hemostasis , Energy Metabolism , Free Radicals , Nitric Oxide , TelencephalonABSTRACT
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