Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection

doi:10.3748/wjg.v27.i37.6248

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World Journal of Gastroenterology

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World J Gastroenterol. Oct 7, 2021; 27(37): 6248-6261
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6248

Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection

Jing-Jing Nie, Ya-Ya Pian, Ji-Hong Hu, Guo-Qing Fan, Lv-Tao Zeng, Qiu-Geng Ouyang, Zhen-Xiang Gao, Zhen Liu, Chen-Chen Wang, Qian Liu, Jian-Ping Cai

Jing-Jing Nie, Ya-Ya Pian, Ji-Hong Hu, Zhen-Xiang Gao, Department of Microbiology, National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Guo-Qing Fan, Lv-Tao Zeng, Zhen Liu, Qian Liu, Jian-Ping Cai, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Qiu-Geng Ouyang, Chen-Chen Wang, Department of Pharmacy, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China

Author contributions: Cai JP provided the research concept; Cai JP, Hu JH, and Nie JJ designed the study; Nie JJ and Pian YY performed the majority of the experiments; Fan GQ, Zeng LT, Ouyang QG, Wang CC, Liu Q, Liu Z, and Gao ZX helped to perform part of the experiments; Nie JJ performed the statistical analysis; Nie JJ and Cai JP wrote the manuscript; all authors approved the final version of the article; Nie JJ and Pian YY contributed equally to this work.

Supported by the National Key R&D Program of China, No. 2018YFC2000300; and CAMS Innovation Fund for Medical Sciences, No. 2018-I2M-1-002.

Institutional animal care and use committee statement: This study was approved by the Ethical Committee of the Institute of Medical Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-201803140206).

Conflict-of-interest statement: The authors declare no conflicts of interest in association with the present study.

Data sharing statement: No additional data are available.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Corresponding author: Jian-Ping Cai, PhD, Professor, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, Dongcheng District, Beijing 100730, China. caijp61@vip.sina.com

Received: March 2, 2021
Peer-review started: March 2, 2021
First decision: April 17, 2021
Revised: April 29, 2021
Accepted: August 9, 2021
Article in press: August 9, 2021
Published online: October 7, 2021
Processing time: 211 Days and 1 Hours

Abstract

BACKGROUND

Shigella flexneri (S. flexneri) is a major pathogen causing acute intestinal infection, but the systematic oxidative damage incurred during the course of infection has not been investigated.

AIM

To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S. flexneri-induced intestinal infection.

METHODS

In this study, a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S. flexneri strains. The changes in white blood cells (WBCs) and cytokine levels in blood and the inflammatory response in the colon were investigated. We also detected the RNA and DNA oxidation in urine and tissues.

RESULTS

S. flexneri infection induced an increase in WBCs, C-reactive protein, interleukin (IL)-6, IL-10, IL-1β, IL-4, IL-17a, IL-10, and tumor necrosis factor α (TNF-α) in blood. Of note, a significant increase in urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), an important marker of total RNA oxidation, was detected after intestinal infection (P = 0.03). The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection. In addition, the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6, TNF-α, IL-10, IL-1β, and IL-17α. Further detection of the oxidation in different tissues showed that S. flexneri infection induced RNA oxidative damage in the colon, ileum, liver, spleen, and brain.

CONCLUSION

Acute infection induced by S. flexneri causes increased RNA oxidative damage in various tissues (liver, spleen, and brain) and an increase of 8-oxo-Gsn, a urinary metabolite. Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.

Keywords: 8-oxo-7,8-dihydroguanosine; Shigella flexneri; Infection; Oxidative damage

Core Tip: Shigella flexneri (S. flexneri) is a major pathogen causing acute intestinal infection, but the systematic oxidative damage incurred during the course of infection has not been investigated. By establishing a Sprague-Dawley rat model with S. flexneri infection in the intestine, we found that 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) levels were markedly increased in the colon, ileum, liver, spleen, and brain after infection, showing that S. flexneri can exacerbate systemic RNA oxidation. The changing trend in levels of urinary 8-oxo-Gsn (as the RNA oxidative metabolites) was consistent with the changes in the white blood cell count, C-reactive protein level, and cytokine levels during infection. Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.