Role of oxidative stress and NFkB in hypoxia-induced pulmonary edema.
Hypoxia is well known to increase the free radical generation in the body, leading to oxidative stress. In the present study, we have determined whether the increased oxidative stress further upregulates the nuclear transcription factor (NFkB) in the development of pulmonary edema. The rats were exposed to hypobaric hypoxia at 7620 m (280 mm Hg) for different durations, that is, 3 hrs, 6 hrs, 12 hrs, and 24 hrs at 25+/-1 degrees C. The results revealed that exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, with time up to 6 hrs (256.38+/-61 rfu/g) as compared with control (143.63+/-60.1 rfu/g). There was a significant increase in reactive oxygen species, lipid peroxidation, and superoxide dismutase levels, with a concurrent decrease in lung glutathione peroxidase activity. There was 13-fold increase in the expression of NFkB level in nuclear fraction of lung homogenates of hypoxic animals over control rats. The DNA binding activity of NFkB was found to be increased significantly (P<0.001) in the lungs of rats exposed to hypoxia as compared with control. Further, we observed a significant increase in proinflammatory cytokines such as IL-1, IL-6, and TNF-alpha with concomitant upregulation of cell adhesion molecules such as ICAM-I, VCAM-I, and P-selectin in the lung of rats exposed to hypoxia as compared with control. Interestingly, pretreatment of animals with curcumin (NFkB blocker) attenuated hypoxia-induced vascular leakage in lungs with concomitant reduction of NFkB levels. The present study therefore reveals the possible involvement of NFkB in the development of pulmonary edema.
Sarada
Sagi
S
Department of Experimental Biology, Defense Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi-54, India. saradasks@gmail.com
Himadri
Patir
P
Mishra
Chitaranjan
C
Geetali
Pradhan
P
Ram
Mastoori Sai
MS
Ilavazhagan
Govindan
G
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D011485:Protein Binding; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D004247:DNA