Serum oxidative/anti-oxidative stress balance is dysregulated in potentially pulmonary hypertensive patients with liver cirrhosis: A case control study

Masako Terao, Akinobu Takaki, Takayuki Maruyama, Hiroki Oe, Tetsuya Yasunaka, Naofumi Tamaki, Kazufumi Nakamura, Takaaki Tomofuji, Takahito Yagi, Hiroshi Sadamori, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Kazuhiro Nouso, Daisuke Ekuni, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Manabu Morita, Hiroshi ItohToshiyoshi Fujiwara, Kazuhide Yamamoto

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

Original languageEnglish
Pages (from-to)2815-2826
Number of pages12
JournalInternal Medicine
Volume54
Issue number22
DOIs
Publication statusPublished - Nov 15 2015

Fingerprint

Liver Cirrhosis
Case-Control Studies
Oxidative Stress
Lung
Hepatopulmonary Syndrome
Serum
Hypertension
Blood Vessels
Nitric Oxide
Oxygen
Tricuspid Valve Insufficiency
Partial Pressure
Vasoconstriction
Oxidants
Nitric Oxide Synthase
Liver Transplantation
Dilatation
Fibrosis
Pressure

Keywords

  • Hepatopulmonary syndrome
  • Liver cirrhosis
  • Oxidative stress
  • Portopulmonary syndrome

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Serum oxidative/anti-oxidative stress balance is dysregulated in potentially pulmonary hypertensive patients with liver cirrhosis : A case control study. / Terao, Masako; Takaki, Akinobu; Maruyama, Takayuki; Oe, Hiroki; Yasunaka, Tetsuya; Tamaki, Naofumi; Nakamura, Kazufumi; Tomofuji, Takaaki; Yagi, Takahito; Sadamori, Hiroshi; Umeda, Yuzo; Shinoura, Susumu; Yoshida, Ryuichi; Nouso, Kazuhiro; Ekuni, Daisuke; Koike, Kazuko; Ikeda, Fusao; Shiraha, Hidenori; Morita, Manabu; Itoh, Hiroshi; Fujiwara, Toshiyoshi; Yamamoto, Kazuhide.

In: Internal Medicine, Vol. 54, No. 22, 15.11.2015, p. 2815-2826.

Research output: Contribution to journalArticle

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abstract = "Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.",
keywords = "Hepatopulmonary syndrome, Liver cirrhosis, Oxidative stress, Portopulmonary syndrome",
author = "Masako Terao and Akinobu Takaki and Takayuki Maruyama and Hiroki Oe and Tetsuya Yasunaka and Naofumi Tamaki and Kazufumi Nakamura and Takaaki Tomofuji and Takahito Yagi and Hiroshi Sadamori and Yuzo Umeda and Susumu Shinoura and Ryuichi Yoshida and Kazuhiro Nouso and Daisuke Ekuni and Kazuko Koike and Fusao Ikeda and Hidenori Shiraha and Manabu Morita and Hiroshi Itoh and Toshiyoshi Fujiwara and Kazuhide Yamamoto",
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T1 - Serum oxidative/anti-oxidative stress balance is dysregulated in potentially pulmonary hypertensive patients with liver cirrhosis

T2 - A case control study

AU - Terao, Masako

AU - Takaki, Akinobu

AU - Maruyama, Takayuki

AU - Oe, Hiroki

AU - Yasunaka, Tetsuya

AU - Tamaki, Naofumi

AU - Nakamura, Kazufumi

AU - Tomofuji, Takaaki

AU - Yagi, Takahito

AU - Sadamori, Hiroshi

AU - Umeda, Yuzo

AU - Shinoura, Susumu

AU - Yoshida, Ryuichi

AU - Nouso, Kazuhiro

AU - Ekuni, Daisuke

AU - Koike, Kazuko

AU - Ikeda, Fusao

AU - Shiraha, Hidenori

AU - Morita, Manabu

AU - Itoh, Hiroshi

AU - Fujiwara, Toshiyoshi

AU - Yamamoto, Kazuhide

PY - 2015/11/15

Y1 - 2015/11/15

N2 - Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

AB - Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH. Methods We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXYadsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a crosssectional study. Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting. Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

KW - Hepatopulmonary syndrome

KW - Liver cirrhosis

KW - Oxidative stress

KW - Portopulmonary syndrome

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