Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

Abstract

Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO 2 and high PaCO 2 , and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA) production assessed in bronchoalveolar lavage) in a sepsis model consisting of intraperitoneal (ip) injection of Escherichia coli and the protective effects of pentoxifylline (PTX). Male Wistar rats (weighing between 270 and 350 g) were injected ip with 10 7 or 10 9 CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group). PaO 2 , PaCO 2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group) and the animals were observed for 6 h. Injection of 10 7 or 10 9 CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05) cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05) in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05) concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05) most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions. Correspondence

Pulmonary Disease in Hamsters Infected with Leptospira interrogans: Histopathologic Findings and Cytokine mRNA Expressions

“…19 Modulation of IL-10 mRNA expression was much less pronounced than that of TNF-a. In contrast to TNF-a, a constitutive expression of IL-10 mRNA was found in control animals, with only moderate modulation along the 28 days of the experiment.…”

“…18 We have previously shown that TNF-a and IL-6 were detected in high levels of bronchoalveolar lavage (BAL) in rats injected intraperitoneally with Escherichia coli . 19 In this study we aimed to evaluate the expression of tissue TNF-a, IL-10, and endothelial nitric-oxide synthesis (eNOS) mRNA levels in an experimental model of Leptospirainduced lung dysfunction, assessed by functional and histologic parameters.…”

Aspectos histomorfológicos e respiratórios em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina

“…Em nosso meio, desenvolvemos um modelo de disfunção pulmonar, com foco infeccioso , que tem mostrado relevância clÍnica no estudo das doenças, tendo ainda a possibilidade de se testar intervenções terapêuticas. Nesse modelo, demonstramos que a pentoxifilina (PTX) reduz as proteínas totais no lavado broncoalveolar de animais sedados e em respiração espontâ-nea, submetidos a infusão intraperitoneal de Escherichia coli (E. coli) 21 . O presente estudo teve como objetivo avaliar as alterações bioquímicas e morfométricas no pulmão de ratos com disfunção pulmonar induzida por sepse e suporte ventilatório tratados com pentoxifilina.…”

“…O presente estudo teve como objetivo avaliar as alterações bioquímicas e morfométricas no pulmão de ratos com disfunção pulmonar induzida por sepse e suporte ventilatório tratados com pentoxifilina. 21 . Consiste na administração intraperitoneal de 1mL/100g de peso corporal (1 mL corresponde a 10 7 unidades formadoras de colônia -UFC), de uma solução de bactérias, essas bactérias foram classificadas pela bioquímica e morfologia como Escherichia coli R-6.…”

Effects of lycopene on the model of oleic acid-induced acute lung injury

“…Plasma and BAL levels of MDA have been shown to increase significantly in experimental studies of acute lung injury (21,22). Septic lung injury models in rats showed the increase in lung tissue MDA levels which decreased after application of N-acetylsistein or methylene blue (18,23).…”