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Open AccessArticle

Serum Levels of Mitochondrial and Microbial Metabolites Reflect Mitochondrial Dysfunction in Different Stages of Sepsis

1
Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Petrovka str., 25-2, 107031 Moscow, Russia
2
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya str., 3, Pushchino, 142290 Moscow Region, Russia
*
Author to whom correspondence should be addressed.
Metabolites 2019, 9(10), 196; https://doi.org/10.3390/metabo9100196
Received: 16 July 2019 / Revised: 16 September 2019 / Accepted: 18 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue Mitochondria and Metabolism in Disorders)
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. View Full-Text
Keywords: sepsis; mitochondrial dysfunction; GC–MS; succinic acid; fumaric acid; itaconic acid; aromatic microbial metabolites; phenylcarboxylic acids; acidosis; succinate dehydrogenase sepsis; mitochondrial dysfunction; GC–MS; succinic acid; fumaric acid; itaconic acid; aromatic microbial metabolites; phenylcarboxylic acids; acidosis; succinate dehydrogenase
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Beloborodova, N.; Pautova, A.; Sergeev, A.; Fedotcheva, N. Serum Levels of Mitochondrial and Microbial Metabolites Reflect Mitochondrial Dysfunction in Different Stages of Sepsis. Metabolites 2019, 9, 196.

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