期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 231, 期 3, 页码 354-363出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2008.05.008
关键词
hypoxia; cerebral vascular leakage; NF kappa B; cobalt; metallothionein; heme oxygenase
资金
- Council of Scientific and Industrial Research, Govt. of India
- Defence Research and Development Organisation, Govt. of India
This study reports the efficacy of cobalt preconditioning in preventing hypobaric hypoxia induced vascular leakage (an indicator of cerebral edema) using male Sprague-Dawley Fats as model system. Exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, reactive oxygen species (ROS), nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There was a marked increase in Nuclear Factor kappa B (NF kappa B) DNA binding activity and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein (MCP-1), Interferon-gamma (IFN-gamma), Interleukin-1 (IL-1), and Tumor Necrosis Factor-alpha (TNF-alpha) and cell adhesion molecules Such as Vascular Cell Adhesion Molecule-1 (VCAM-1), and P-selectin. Chemical preconditioning by cobalt for 7 days (12.5 mg Co/kg b.w., Oral) significantly attenuated cerebral vascular leakage and the expression of inflammatory mediators induced by hypoxia. Administration of NF kappa B inhibitor, curcumin (50 mg/kg b.w.: i.p.) appreciably inhibited hypoxia induced vascular leakage indicating the involvement of NF kappa B in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage indicating that cobalt per se did not have an effect on NF kappa B. The lower levels of NF kappa B observed in the brains of cobalt administered animals might be due to higher levels of antioxidant and anti-inflammatory, proteins (hemeoxygenase-1 and metallothionein). To conclude cobalt preconditioning inhibited hypobaric hypoxia induced cerebral vascular leakage by lowering NF kappa B DNA binding activity and its regulated pro-inflammatory mediators. This is contemplated to be mediated by cobalt induced reduction in ROS/NO and increase in HO-1 and MT. (C) 2008 Elsevier Inc. All rights reserved.
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