Oxidative stress and the production of intracellular
reactive oxygen species (ROS) have been implicated in the pathogenesis of
sepsis. In excess, oxidative stress is not deemed an unbalanced biochemical reaction in the
critically ill rats, but it is a key pathological factor in driving systemic inflammatory response that can result in
multiple organ failure in
sepsis. Thus, we aimed to explore whether
antioxidant nutrients could reduce or delay the oxidative stress condition of
sepsis rats, and then play a prospective role in the oxidative stress condition of critical disease. In this investigation, the ability of exogenous and
endogenous antioxidant nutrients (ascorbate,
taurine and
glutathione) to prevent
sepsis-induced changes in liver injury was examined using a rat model of
sepsis induced by cecal
ligation and
puncture (CLP), and the underlying mechanisms were also investigated. The effects of three
antioxidants on
sepsis were assessed based on biochemical assays in combination with an NMR-based metabolomics approach and correlation network analysis. Our results suggested that ascorbate,
taurine and
glutathione had broadly similar protective effects on reducing oxidative stress. Compared with CLP rats,
antioxidant-treated rats exhibited alleviated (P<.05) organ dysfunction and improved liver pathology. Moreover,
taurine showed a better efficacy compared with ascorbate and
glutathione, evidenced by significantly reversed metabolomics profiles toward normal state. Under conditions of
sepsis,
antioxidants suppressed inflammatory responses by restraining key signaling pathways, including the redox-sensitive
transcription factor pathways of NF-κB and MAPK. Collectively, our findings suggested that
antioxidant nutrients exerted beneficial effects on septic rats via protecting mitochondrial.