Effect of antioxidants on apoptosis and cytokine release in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide.
The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the developing lung. Our goals were to evaluate the effect of antioxidants (AO) on apoptosis and release of cytokines in freshly isolated FTIIP (day-19) in the presence of 95% O2 and/or nitric oxide (NO). There was increased apoptosis in FTIIP exposed to hyperoxia alone and in combination with NO; this was significantly attenuated (p < 0.01) in the presence of 3 AO, namely grape seed proanthocyanidin extract (GSPE), superoxide dismutase (SOD) and catalase. The anti-inflammatory cytokine IL-10 has been shown to have a role in ameliorating tissue damage owing to persistent inflammation. The release of IL-10 was significantly decreased (p < 0.01) in the presence of GSPE and catalase, compared to control. Addition of SOD led to increased IL-10 compared to GSPE or catalase (p < 0.01) or the combination of GSPE + SOD + catalase (p < or = 0.01). Thus, in our in vitro model of hyperoxic and NO mediated injury to FTIIP, protection from apoptotic cell death with the addition of AO was associated with varying levels of IL-10 release. Our data suggest that the use of SOD and/or IL-10 may decrease hyperoxic lung injury by decreasing apoptosis. Further studies are needed to understand the mode of protection from catalase and GSPE.
Johnson-Varghese
L
L
Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA.
Brodsky
N
N
Bhandari
V
V
D000332:Aerobiosis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005865:Gestational Age; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D016207:Cytokines; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D010100:Oxygen