Systemic RNA oxidation can be used as an index of clinical infection and prognosis in a Vibrio parahaemolyticus Challenge Rat Model

Background: More and more evidence supports the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as an index of clinical infection and prognosis in a Vibrio parahaemolyticus challenge rat model. In this study, twenty-four specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group. An LC-MS/MS-based system was established to determine the 8-oxo-dGsn and 8-oxo-Gsn contents of urine samples. The immunohistochemistry (IHC) was used to determine the 8-oxoguanine in nuclear DNA and in cellular RNA of different tissues of rats. Hematoxylin-eosin (H&E) stain was used to analyze intestinal inflammation. Sysmex XS-1000i hematology was used to analyze WBCs in blood. Luminex and ELISA were used to detect the level of inflammatory factors in serum. In addition, body temperatures, body weights, bacterial burden of Vibrio parahaemolyticus were also detected. Results: The level of urinary and tissular 8-oxo-Gsn rather than 8-oxo-dGsn was significantly increased after infection with V. parahaemolyticus compared with PBS control. Stimultaneously, intestinal inflammation, the numbers of white blood cells (WBCs) and inflammatory factors (including CRP, IL-6, IL-1β, TNF-α, IL-10 and IL-17A) were increased sharply. What is clinical significance is that the trend of urinary 8-oxo-Gsn was consistent with WBCs or inflammation. It is more important that the concentration of urinary 8-oxo-Gsn in the infection group was positively correlated with WBCs and inflammatory cytokines. Conclusion: Our results demonstrated that 8-oxo-Gsn can be used as a more effective biomarker of clinical infection and prognosis compared with classic clinical indicators such as IL-6 and TNF-α.