metallothionein and Pulmonary-Edema

Exposure to high altitude results in hypobaric hypoxia which is considered as an acute physiological stress and often leads to high altitude maladies such as high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The best way to prevent high altitude injuries is hypoxic preconditioning which has potential clinical usefulness and can be mimicked by cobalt chloride. Preconditioning with cobalt has been reported to provide protection in various tissues against ischemic injury. However, the effect of preconditioning with cobalt against high altitude induced pulmonary edema has not been investigated in vivo. Therefore, in the present study, rats pretreated with saline or cobalt (12.5mg/kg body weight) for 7days were exposed to hypobaric hypoxia of 9142m for 5h at 24°C. Formation of pulmonary edema was assessed by measuring transvascular leakage of sodium fluorescein dye and lung water content. Total protein content, albumin content, vascular endothelial growth factor (VEGF) and cytokine levels were measured in bronchoalveolar lavage fluid. Expression of HO-1, MT, NF-κB DNA binding activity and lung tissue pathology were evaluated to determine the effect of preconditioning on HAPE. Hypobaric hypoxia induced increase in transvascular leakage of sodium fluorescein dye, lung water content, lavage total protein, albumin, VEGF levels, pro-inflammatory cytokine levels, tissue expression of cell adhesion molecules and NF-κB DNA binding activity were reduced significantly after hypoxic preconditioning with cobalt. Expression of anti-inflammatory protein HO-1, MT, TGF-β and IL-6 were increased after hypoxic preconditioning. These data suggest that hypoxic preconditioning with cobalt has protective effect against HAPE.

Topics: Albumins; Altitude; Animals; Bronchoalveolar Lavage Fluid; Capillary Permeability; Cell Adhesion Molecules; Cobalt; Cytokines; DNA; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Hypoxia; Lung; Male; Metallothionein; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Transcription Factor RelA; Vascular Endothelial Growth Factor A

The effect of endotoxin on serum and lung and liver lipid peroxidation, as measured by thiobarbituric acid reactants (TBARs), as well as on lung and liver metallothionein (MT) has been studied in the rat. Endotoxin consistently increased serum and liver TBARs in a time-response manner. The increase in the serum preceded that in the liver, with peaks 3-6 h and 24 h after endotoxin administration, respectively. In contrast, lung TBARs levels did not increase regardless of the experimental approaches studied, suggesting that the rat is not a good model for the adult respiratory distress syndrome. Endotoxin increased both lung and liver MT levels in a time-response manner, although to a lesser degree in the former than in the latter tissue, indicating that this protein may have a significant role in the response of the organism to a septic insult.

Topics: Animals; Disease Models, Animal; Drug Administration Routes; Endotoxins; Lipid Peroxidation; Liver; Lung; Male; Metallothionein; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances