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Regular Manuscript

Role of oxidative stress and NFkB in hypoxia induced pulmonary edema

¹ DIPAS

^* To whom correspondence should be addressed. E-mail: saradasks{at}yahoo.com.

	Abstract

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 up regulates the nuclear transcription factor (NFkB) in the development of pulmonary edema. The rats were exposed to hypobaric hypoxia at 7620m (280mmHg) for different durations viz. 3h, 6h, 12h, and 24h at 25±1oC . The results revealed that, exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage with time up to 6h (256.38±61 r.f.u/gm) as compared to control (143.63±60.1 r.f.u/gm). There was a significant increase in reactive oxygen species (ROS), lipid peroxidation (MDA) and superoxide dismutase (SOD) levels with a concurrent decrease in lung glutathione peroxidase (GPx) 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 to control. Further, we observed a significant increase in proinflammatory cytokines such as IL-1, IL-6, and TNF- with concomitant up-regulation of cell adhesion molecules such as ICAM-I, VCAM-I and P-selectin in the lung of rats exposed to hypoxia as compared to control. Interestingly, pre-treatment of animals with curcumin (NFkB blocker) attenuated hypoxia induced vascular leakage in lungs with concomitant reduction of NF-kB levels. The present study therefore reveals possible involvement NFkB in the development of pulmonary edema.

Key Words: HAPE, NFkB, Oxidative stress, Pro-inflammatory cytokines, Hypoxia, inflammation