Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients

Author:

Tsuge Mitsuru1ORCID,Ichihara Eiki2ORCID,Hasegawa Kou3,Kudo Kenichiro4,Tanimoto Yasushi5ORCID,Nouso Kazuhiro6ORCID,Oda Naohiro7,Mitsumune Sho4,Kimura Goro5,Yamada Haruto8,Takata Ichiro7,Mitsuhashi Toshiharu9ORCID,Taniguchi Akihiko2,Tsukahara Kohei10,Aokage Toshiyuki10,Hagiya Hideharu3ORCID,Toyooka Shinichi11,Tsukahara Hirokazu1,Maeda Yoshinobu12

Affiliation:

1. Department of Pediatrics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan

2. Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama 700-8558, Japan

3. Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan

4. Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama 701-1192, Japan

5. Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama 701-0304, Japan

6. Department of Gastroenterology, Okayama City Hospital, Okayama 700-0962, Japan

7. Department of Internal Medicine, Fukuyama City Hospital, Fukuyama 721-0971, Japan

8. Department of Infectious Disease, Okayama City Hospital, Okayama 700-0962, Japan

9. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama 700-8558, Japan

10. Department of Emergency, Critical Care and Disaster Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan

11. Department of General Thoracic Surgery and Breast and Endocrine Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan

12. Department of Hematology, Oncology and Respiratory Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan

Abstract

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

Funder

Okayama University

Publisher

MDPI AG

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