Lipid peroxidation precedes TNF and PDGF release in alveolar macrophage of the experimental pulmonary fibrosis rats

AIM:To evaluate the role of alveolar macrophage(AM)lipid peroxidation in bleomycin(BLM)-induced TNF-and PDGF release from AM in rats.METHODS:Male SD rats were intratracheal y instilled with saline or BLM(5 mg/kg body weight), and AM were isolated and analyzed for malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)following 1, 3, 7, 14 or 28 day(s).Simultaneously, TNF-and platelet-derived growth factor(PDGF)were also determined in AM-conditoned media by ELISA and bioassay respectively.RESULTS:(1)MDA in AM was markedly increased on day1, peaked on day 3 and then decreased to near control level on day 7;on the other hand, GSH-Px activity in AM were decreased to non-detectable levels during day 1-7 after BLM instillat ion, returned to the control level by day 14.(2)TNF-and PDGF were increased significantly from the third day on and then exhibited a consectutive changes.(3)AM lipid peroxidation preceded TNF-and PDGF release.CONCLUSION:Prior oxidative changes leading to AM lipid peroxidation, depletion of antioxidative pool might be essential for the subsequent mediators release in BLM-induced pulmonary fibrosis.