Toxic oxygen free radicals have been implicated as important pathologic mediators in many clinical disorders. We discuss the chemistry of oxygen radical production and the roles of iron an...

Oxygen Radicals and Human Disease

Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner. Myd88(-/-) and Tlr4(-/-)Tlr2(-/-) mice showed impaired transepithelial migration of inflammatory cells but decreased survival and enhanced epithelial cell apoptosis after lung injury. Lung epithelial cell-specific overexpression of high-molecular-mass hyaluronan was protective against acute lung injury. Furthermore, epithelial cell-surface hyaluronan was protective against apoptosis, in part, through TLR-dependent basal activation of NF-kappaB. Hyaluronan-TLR2 and hyaluronan-TLR4 interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity and promote recovery from acute lung injury.

Regulation of lung injury and repair by Toll-like receptors and hyaluronan.

The importance of free radicals and catalytic metal ions in human diseases

Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection.

Nas últimas décadas, foram realizadas inúmeras pesquisas para esclarecer o papel dos radicais livres em processos fisiopatológicos como envelhecimento, câncer, aterosclerose, inflamação, etc. Ao abrirmos um periódico, com freqüência, encontramos temas relacionados a radicais livres, que, por seu caráter multidisciplinar, têm atraído a atenção de pesquisadores de várias áreas. No entanto, os artigos desta linha de pesquisa, muitas vezes, causam desinteresse no leitor não-especializado, porque estão mergulhados num mundo bioquímico de difícil entendimento. O objetivo do presente artigo é fornecer conceitos importantes a esses leitores, com a finalidade de desmistificar o tema.

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Radicais livres: conceitos, doenças relacionadas, sistema de defesa e estresse oxidativo

Intact erythrocytes placed into the tracheobronchial tree of hyperoxic rats dramatically improved their chances for survival. Over 70 percent of the animals so treated survived more than 12 days during continuous exposure to 95 percent oxygen, whereas all of the control animals died within 96 hours. Lungs from erythrocyte-protected rats showed almost none of the morphologic damage suffered by untreated animals. Erythrocytes containing cyanomethemoglobin were as beneficial as normal erythrocytes, but cells in which glutathione was partially blocked were significantly less protective. Analogous results were obtained in vitro: 51Cr-labeled target cells released 70 to 90 percent of their label when exposed briefly to hydrogen peroxide or to toxic oxygen species generated by phorbol ester-stimulated neutrophils. Addition of intact erythrocytes decreased release by approximately 75 percent, but significantly less than this if red blood cell glutathione was partially blocked. These results suggest that insufflated erythrocytes, through their recyclable glutathione, protect rats from toxic oxygen species engendered by hyperoxia.

https://science.sciencemag.org/content/sci/227/4688/756.full.pdf

Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione

Human neutrophils (PMN), when stimulated with such chemotaxins as phorbol myristate acetate (PMA), destroy erythrocytes

/pdf/critical-role-of-iron-and-lactoferrin-33vzs8bm3v.pdf

B. Sweder van Asbeck

Papers

Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione

Critical Role of Iron and Lactoferrin