Pentoxifylline attenuates oxygen-induced lung injury.
Patients requiring mechanical ventilation can develop severe pulmonary injury. Although pentoxifylline (PTX) is known to attenuate endotoxin and tumor necrosis factor (TNF)-induced lung injury, as well as decrease interleukin-6 (IL-6) levels following hemorrhage and resuscitation, it remains unknown if this agent has any beneficial effects against O2-induced lung injury. The aim of this study, therefore, was to determine if PTX attenuates pulmonary oxygen toxicity. To investigate this, male Sprague-Dawley rats were injected subcutaneously with 1 ml saline or 1 ml PTX (50 mg/kg) and immediately exposed to either 21% O2 or > or = 95% O2 for 52 hr. The animals were then reweighed and euthanized. Pleural fluid was collected, blood samples were obtained, and lung lavage was performed. Lactate dehydrogenase (LDH) activity, protein content, and IL-6 concentrations were determined in the lavage fluid and serum. The supernatant LDH activity, protein content, pleural fluid accumulation, and IL-6 concentration were significantly decreased (P < 0.05) in those animals pretreated with PTX prior to exposure to hyperoxia compared to those animals exposed to hyperoxia and not treated. Furthermore, the hematocrit and serum IL-6 concentration were also decreased in the treated group and not significantly different from the controls. Thus, PTX appears to attenuate O2-induced lung injury and may play a role in protecting those patients at risk for developing pulmonary oxygen toxicity.
Department of Surgery, Michigan State University, East Lansing 48824.
H J
HJ
Lindsey
J M
JM
Kisala
A
A
Ayala
D
D
Lehman
C D
CD
Herdon
I H
IH
Chaudry
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D010431:Pentoxifylline / Q000494:pharmacology*; D010994:Pleura / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D010100:Oxygen; D010431:Pentoxifylline