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Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung.

Aoki T, Yamasawa F, Kawashiro T, Shibata T, Ishizaka A, Urano T, Okada Y - Respir. Res. (2008)

Bottom Line: These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure.However, these changes are successfully compensated even with continuous exposure to low-dose oxygen.We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Respiratory Division, Department of Internal Medicine, School of Medicine, Tokai University, Isehara, Japan. ZWQ00221@nifty.ne.jp

ABSTRACT

Background: The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.

Methods: Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.

Results: The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.

Conclusion: These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

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Sections of peripheral parts of the lungs stained with hematoxylin-eosin. Panels A, B, C, D and E represent pre- and, 2, 4, 8 and 16 week-exposure to 40% oxygen. Neither discernible injury nor architectural disorganization can be seen in any of these groups. Bar = 100 μm.
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Figure 9: Sections of peripheral parts of the lungs stained with hematoxylin-eosin. Panels A, B, C, D and E represent pre- and, 2, 4, 8 and 16 week-exposure to 40% oxygen. Neither discernible injury nor architectural disorganization can be seen in any of these groups. Bar = 100 μm.

Mentions: Although the image analyzing system revealed that the fibrous tissue in the aniline blue stained section was increased with 2 weeks exposure to 40% oxygen, neither discernible injury nor architectural disorganization was observed in these groups (Fig. 9). In the 90% oxygen groups, inflammatory cell infiltration was recognized after 72 hours of exposure, and alveolar septal destruction was apparent by 96 hours (Fig. 10). Diffuse alveolar damage was apparent after 120 hours of exposure.


Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung.

Aoki T, Yamasawa F, Kawashiro T, Shibata T, Ishizaka A, Urano T, Okada Y - Respir. Res. (2008)

Sections of peripheral parts of the lungs stained with hematoxylin-eosin. Panels A, B, C, D and E represent pre- and, 2, 4, 8 and 16 week-exposure to 40% oxygen. Neither discernible injury nor architectural disorganization can be seen in any of these groups. Bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2377243&req=5

Figure 9: Sections of peripheral parts of the lungs stained with hematoxylin-eosin. Panels A, B, C, D and E represent pre- and, 2, 4, 8 and 16 week-exposure to 40% oxygen. Neither discernible injury nor architectural disorganization can be seen in any of these groups. Bar = 100 μm.
Mentions: Although the image analyzing system revealed that the fibrous tissue in the aniline blue stained section was increased with 2 weeks exposure to 40% oxygen, neither discernible injury nor architectural disorganization was observed in these groups (Fig. 9). In the 90% oxygen groups, inflammatory cell infiltration was recognized after 72 hours of exposure, and alveolar septal destruction was apparent by 96 hours (Fig. 10). Diffuse alveolar damage was apparent after 120 hours of exposure.

Bottom Line: These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure.However, these changes are successfully compensated even with continuous exposure to low-dose oxygen.We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Respiratory Division, Department of Internal Medicine, School of Medicine, Tokai University, Isehara, Japan. ZWQ00221@nifty.ne.jp

ABSTRACT

Background: The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.

Methods: Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.

Results: The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.

Conclusion: These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

Show MeSH
Related in: MedlinePlus