Pentoxifylline does not protect against hyperoxic lung injury in rats

Abstract

P Pe en nt to ox xi if fy yl ll li in ne e d do oe es s n no ot t p pr ro ot te ec ct t a ag ga ai in ns st th hy yp pe er ro ox xi ic c l lu un ng g i in nj ju ur ry y i in n r ra at ts s The drug pentoxifylline has been shown to have a protective effect in other models of lung injury. We sought to determine whether pentoxifylline protects against hyperoxic lung injury in rats by decreasing the accumulation of neutrophils within the lung. A total of 84 rats were studied. Twenty four rats were randomized into four groups. Two groups of rats were pretreated for 48 h with either pentoxifylline (20 mg·kg -1 ) or saline, and then exposed to >95% O 2 for 60 h while treatments continued. Two groups of control rats received the same treatment regimens as the O 2 -exposed animals, but breathed room air. Neutrophil accumulation in the lung was quantified both by histology and myeloperoxidase activity.Lung neutrophil accumulation increased in the oxygen-exposed group receiving pentoxifylline as compared to oxygen-or air-exposed rats receiving saline injections. Total glutathione was higher in lung homogenates from the hyperoxic, pentoxifylline-treated group than in homogenates from the other three groups. To study survival, 60 rats were exposed to >95% O 2 for 120 h, 30 rats were pretreated with pentoxifylline, and 30 received saline. Survival after 120 h of exposure to hyperoxia was not altered by pentoxifylline treatment (pentoxifylline treated: 6 out of 30 survived; saline treated: 2 out of 30 survived).We conclude that pentoxifylline does not reduce mortality or lung injury in rats exposed to hyperoxia and is associated with an increase in lung neutrophil accumulation.

Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction

“…Support for this hypothesis is the fact that in some circumstances, PTX may enhance neutrophil migration and accumulation in lung tissues at concentrations sufficient to induce an anti-inflammatory effect. 38,39 The concentration of PTX required for inhibition of cytokine production in live horses is unknown, but PTX concentrations lower than those obtained in the study reported here have inhibited the production of proinflammatory cytokines in several in vitro equine models. 10,23 Based on results of the study reported here, it can be concluded that the administration of PTX improves respiratory function of RAO-affected horses.…”

Animal models of acute lung injury

“…The initial event appears to be damage to the capillary endothelium, followed by platelet adhesion and PMN accumulation in the capillary vessels and interstitium (13,82). Eventually, alveolar epithelial injury occurs, with an increase in microvascular permeability measured as wet-to-dry (W/D) ratios and migration of neutrophils into the air spaces, as evidenced by increase in total numbers in BAL fluid (18,20,102,148). The pulmonary architecture is preserved during this early phase (82).…”

“…In rats and mice, exposure to 100% O 2 for 40 -50 h results in ALI, and longer exposure (60 -70 h) results in death (13,18,63,148). Survival after exposure to O 2 is age dependent, as neonates are more tolerant to hyperoxia and survive for up to 7 days (67).…”

Pentoxifylline and tumour necrosis factor-induced lung injury

“…This issue of the Journal contains an article by NAURECKAS et al [19] reporting that POF does not protect against hyperoxic lung injury in rats. This paper is of great interest, because it demonstrates that the protective effect of POF depends on the cause of lung injury.…”