Background: The bacterial endotoxin lipopolysaccharide (LPS) was the classic inducer to establish many inflammatory disease models, especially multiple organ injury. Evidences indicated that the mechanism that causes inflammation response is not just related to cytokine release. The main aim of this study was to better elucidate the possible links between metabolic changes and the pathogenesis of LPS-induced acute liver and kidney in order to understand the mechanisms and screening therapeutic targets for developing early diagnostic strategies and treatments.
Methods: An experimental rat model was established by intraperitoneal injection of 10 mg/kg LPS. An untargeted metabolomics analysis of the serum in the LPS and control groups was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). LPS-induced pathological damage in the lungs, liver, kidneys, and colon was observed, along with changes in biochemical indexes, indicating that there was a severe inflammatory response in many organs after administration of LPS for 8 h. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed distinct separation in the serum metabolite profiles between the LPS and control groups, indicating significant changes in endogenous metabolites.
Results: The untargeted metabolomics analysis showed that there were 127 significantly different serum metabolites and 53 altered pathways after LPS administration, including pathways related to the metabolism of D-glutamine and D-glutamate, taurine and hypotaurine, beta-alanine, glutathione, and butanoate, which are involved in the inflammatory response, oxidative stress, and amino acid metabolism.
Conclusion: The study suggested that LPS-induced acute liver and kidney injury mainly involves inflammatory response, oxidative stress, and protein synthesis, finally causing multi-organ damage. Correcting the disturbances to the metabolites and metabolic pathways may help to prevent and/or treat LPS-induced acute liver and kidney damage.
Keywords: untargeted metabolomics, LPS, acute kidney injury, acute liver injury, amino acid metabolism