Mechanisms of
mitochondrial dysfunction in
sepsis are being extensively studied in recent years. During our study, concentrations of microbial phenolic
acids and mitochondrial metabolites (succinic, α-ketoglutaric, fumaric, itaconic
acids) as indicators of
sepsis and
mitochondrial dysfunction, respectively, are measured by gas chromatography-mass spectrometry (GC-MS) in the blood of
critically ill patients at the early and late stages of documented
sepsis. The increase in levels of some phenylcarboxylic (phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), p-hydroxyphenyllactic (p-HPhAA))
acids (PhCAs), simultaneously with a rise in levels of mitochondrial
dicarboxylic acids, are mainly detected during the late stage of
sepsis, especially
succinic acid (up to 100-1000 µM).
Itaconic acid is found in low concentrations (0.5-2.3 µM) only at early-stage
sepsis. PhCAs in vitro inhibits
succinate dehydrogenase (SDH) in isolated mitochondria but, unlike
itaconic acid which acts as a competitive inhibitor of SDH, microbial metabolites most likely act on the
ubiquinone binding site of the respiratory chain. A close correlation of the level of
succinic acid in serum and
sepsis-induced organ dysfunction is revealed, moreover the most significant correlation is observed at high concentrations of phenolic microbial metabolites (PhCAs) in late-stage
sepsis. These data indicate the promise of such an approach for early detection, monitoring the progression of organ dysfunction and predicting the risk of non-survival in
sepsis.