Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects

Background: Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI. Methods: Lung...

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Main Authors: Wen-Fang Tian, Ping Weng, Qiong Sheng, Jun-Liang Chen, Peng Zhang, Ji-Ru Zhang, Bin Du, Min-Chen Wu, Qing-Feng Pang, Jian-Jun Chu
Format: Article
Language:English
Published: Wolters Kluwer 2017-01-01
Series:Chinese Medical Journal
Subjects:
Online Access:http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=859;epage=865;aulast=Tian
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author Wen-Fang Tian
Ping Weng
Qiong Sheng
Jun-Liang Chen
Peng Zhang
Ji-Ru Zhang
Bin Du
Min-Chen Wu
Qing-Feng Pang
Jian-Jun Chu
author_facet Wen-Fang Tian
Ping Weng
Qiong Sheng
Jun-Liang Chen
Peng Zhang
Ji-Ru Zhang
Bin Du
Min-Chen Wu
Qing-Feng Pang
Jian-Jun Chu
author_sort Wen-Fang Tian
collection DOAJ
description Background: Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI. Methods: Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment. Results: Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P< 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P< 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P< 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P< 0.001, and P< 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P< 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-β) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P< 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group). Conclusion: BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.
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spelling doaj.art-59a6e905aa6f4d7691806ea48b2bb8b12022-12-22T00:16:08ZengWolters KluwerChinese Medical Journal0366-69992017-01-01130785986510.4103/0366-6999.202735Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic EffectsWen-Fang TianPing WengQiong ShengJun-Liang ChenPeng ZhangJi-Ru ZhangBin DuMin-Chen WuQing-Feng PangJian-Jun ChuBackground: Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI. Methods: Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment. Results: Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P< 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P< 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P< 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P< 0.001, and P< 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P< 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-β) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P< 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group). Conclusion: BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=859;epage=865;aulast=TianApoptosis; Biliverdin; Ischemia-reperfusion Injury; Lung; Pro-inflammatory Cytokines
spellingShingle Wen-Fang Tian
Ping Weng
Qiong Sheng
Jun-Liang Chen
Peng Zhang
Ji-Ru Zhang
Bin Du
Min-Chen Wu
Qing-Feng Pang
Jian-Jun Chu
Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
Chinese Medical Journal
Apoptosis; Biliverdin; Ischemia-reperfusion Injury; Lung; Pro-inflammatory Cytokines
title Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
title_full Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
title_fullStr Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
title_full_unstemmed Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
title_short Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects
title_sort biliverdin protects the isolated rat lungs from ischemia reperfusion injury via antioxidative anti inflammatory and anti apoptotic effects
topic Apoptosis; Biliverdin; Ischemia-reperfusion Injury; Lung; Pro-inflammatory Cytokines
url http://www.cmj.org/article.asp?issn=0366-6999;year=2017;volume=130;issue=7;spage=859;epage=865;aulast=Tian
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