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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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Type III collagenolytic enzyme activity. Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly increased as compared to that in the 21% oxygen 2 week-exposure group. This increase was, however, not significantly different as compared to that in the pre-exposure group. At 4, 8 and 16 week-exposure periods, there were no differences in type III collagenolytic enzyme activity between the 40% and the 21% exposure groups, or between the 40% and the pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure groups was decreased as compared to that in the 40% oxygen 2 week-exposure group. There was no significant difference among the 90% oxygen exposure groups. Values are expressed as means ± SD; n = 8 in the pre-exposure group; n = 7 (2 weeks), 10 (4 weeks), 6 (8 weeks) and 6 (16 weeks) in the 40% oxygen exposure groups; n = 5 (2 weeks), 8 (4 weeks), 5 (8 weeks) and 6 (16 weeks) in the 21% oxygen exposure groups; n = 5 (72 hours), 5 (96 hours) and 5 (120 hours) in the 90% oxygen exposure groups. * p < 0.05 as compared to the value of the 21% oxygen exposure duration-matched control. ++ p < 0.01 as compared to the value of the 40% oxygen 2 week-exposure group.
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Figure 6: Type III collagenolytic enzyme activity. Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly increased as compared to that in the 21% oxygen 2 week-exposure group. This increase was, however, not significantly different as compared to that in the pre-exposure group. At 4, 8 and 16 week-exposure periods, there were no differences in type III collagenolytic enzyme activity between the 40% and the 21% exposure groups, or between the 40% and the pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure groups was decreased as compared to that in the 40% oxygen 2 week-exposure group. There was no significant difference among the 90% oxygen exposure groups. Values are expressed as means ± SD; n = 8 in the pre-exposure group; n = 7 (2 weeks), 10 (4 weeks), 6 (8 weeks) and 6 (16 weeks) in the 40% oxygen exposure groups; n = 5 (2 weeks), 8 (4 weeks), 5 (8 weeks) and 6 (16 weeks) in the 21% oxygen exposure groups; n = 5 (72 hours), 5 (96 hours) and 5 (120 hours) in the 90% oxygen exposure groups. * p < 0.05 as compared to the value of the 21% oxygen exposure duration-matched control. ++ p < 0.01 as compared to the value of the 40% oxygen 2 week-exposure group.

Mentions: Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly higher than that in the 21% oxygen 2 week-exposure group (Fig. 6). This increase was, however, not significantly different as compared to that in the pre-exposure group. After 4, 8 or 16 weeks of exposure, there were no differences in type III collagenolytic enzyme activity between the 40% and 21% exposure groups, or between the 40% and pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure group was lower than that in the 40% oxygen 2 week-exposure group. There were no significant differences among the 90% oxygen exposure groups.


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)

Type III collagenolytic enzyme activity. Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly increased as compared to that in the 21% oxygen 2 week-exposure group. This increase was, however, not significantly different as compared to that in the pre-exposure group. At 4, 8 and 16 week-exposure periods, there were no differences in type III collagenolytic enzyme activity between the 40% and the 21% exposure groups, or between the 40% and the pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure groups was decreased as compared to that in the 40% oxygen 2 week-exposure group. There was no significant difference among the 90% oxygen exposure groups. Values are expressed as means ± SD; n = 8 in the pre-exposure group; n = 7 (2 weeks), 10 (4 weeks), 6 (8 weeks) and 6 (16 weeks) in the 40% oxygen exposure groups; n = 5 (2 weeks), 8 (4 weeks), 5 (8 weeks) and 6 (16 weeks) in the 21% oxygen exposure groups; n = 5 (72 hours), 5 (96 hours) and 5 (120 hours) in the 90% oxygen exposure groups. * p < 0.05 as compared to the value of the 21% oxygen exposure duration-matched control. ++ p < 0.01 as compared to the value of the 40% oxygen 2 week-exposure group.
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Figure 6: Type III collagenolytic enzyme activity. Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly increased as compared to that in the 21% oxygen 2 week-exposure group. This increase was, however, not significantly different as compared to that in the pre-exposure group. At 4, 8 and 16 week-exposure periods, there were no differences in type III collagenolytic enzyme activity between the 40% and the 21% exposure groups, or between the 40% and the pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure groups was decreased as compared to that in the 40% oxygen 2 week-exposure group. There was no significant difference among the 90% oxygen exposure groups. Values are expressed as means ± SD; n = 8 in the pre-exposure group; n = 7 (2 weeks), 10 (4 weeks), 6 (8 weeks) and 6 (16 weeks) in the 40% oxygen exposure groups; n = 5 (2 weeks), 8 (4 weeks), 5 (8 weeks) and 6 (16 weeks) in the 21% oxygen exposure groups; n = 5 (72 hours), 5 (96 hours) and 5 (120 hours) in the 90% oxygen exposure groups. * p < 0.05 as compared to the value of the 21% oxygen exposure duration-matched control. ++ p < 0.01 as compared to the value of the 40% oxygen 2 week-exposure group.
Mentions: Type III collagenolytic enzyme activity in the 40% oxygen 2 week-exposure group was significantly higher than that in the 21% oxygen 2 week-exposure group (Fig. 6). This increase was, however, not significantly different as compared to that in the pre-exposure group. After 4, 8 or 16 weeks of exposure, there were no differences in type III collagenolytic enzyme activity between the 40% and 21% exposure groups, or between the 40% and pre-exposure groups. Type III collagenolytic activities in the 40% oxygen 8 week-exposure group was lower than that in the 40% oxygen 2 week-exposure group. There were no significant differences among the 90% oxygen exposure groups.

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