Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration

Saito, Yu; Morine, Yuji; Iwahashi, Shuichi; Ikemoto, Tetsuya; Imura, Satoru; Yamanaka-Okumura, Hisami; Hirayama, Akiyoshi; Soga, Tomoyoshi; Tomita, Masaru; Shimada, Mitsuo

doi:10.1002/ags3.12058

Cited by 11 publications

(8 citation statements)

References 22 publications

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“…In the last two decades, these analytical methods have been advanced and optimized to enable disease phenotyping and biomarker identification, and they have been increasingly applied in clinical settings [19,20]. We previously reported on the use of an advanced technique, capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS), to monitor changes in liver metabolites following hepatectomy with ischemia reperfusion [21]. Several studies have investigated alterations in the metabolome during hepatocarcinogenesis and identified several candidate metabolic biomarkers that could potentially discriminate between liver diseases, including HCC [22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis

et al. 2022

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Metabolomics, defined as the comprehensive identification of all small metabolites in a biological sample, has the power to shed light on phenotypic changes associated with various diseases, including cancer. To discover potential metabolomic biomarkers of hepatocellular carcinoma (HCC), we investigated the metabolomes of tumor and non-tumor tissue in 20 patients with primary HCC using capillary electrophoresis-time-of-flight mass spectrometry. We also analyzed blood samples taken immediately before and 14 days after hepatectomy to identify associated changes in the serum metabolome. Marked changes were detected in the different quantity of 61 metabolites that could discriminate between HCC tumor and paired non-tumor tissue and additionally between HCC primary tumors and colorectal liver metastases. Among the 30 metabolites significantly upregulated in HCC tumors compared with non-tumor tissues, 10 were amino acids, and 7 were essential amino acids (leucine, valine, tryptophan, isoleucine, methionine, lysine, and phenylalanine). Similarly, the serum metabolomes of HCC patients before hepatectomy revealed a significant increase in 16 metabolites, including leucine, valine, and tryptophan. Our results reveal striking differences in the metabolomes of HCC tumor tissue compared with non-tumor tissue, and identify the essential amino acids leucine, valine, and tryptophan as potential metabolic biomarkers for HCC.

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Section: Introductionmentioning

confidence: 99%

Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis

et al. 2022

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“…There was also significant alteration of the TCA cycle, and this resulted in aberrant levels of citric acid, fumaric acid, and malic acid. It was recently reported that a significant decline in metabolite levels was found in the first half of the TCA cycle 16 . The OPLS-DA model revealed that the metabolites contributed most to the metabolic features of the 90% hepatectomy group.…”

Section: Discussionmentioning

confidence: 99%

Explorative study of serum biomarkers of liver failure after liver resection

Yoon

Kwon

et al. 2020

Sci Rep

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conventional biochemical markers have limited usefulness in the prediction of early liver dysfunction. We, therefore, tried to find more useful liver failure biomarkers after liver resection that are highly sensitive to internal and external challenges in the biological system with a focus on liver metabolites. Twenty pigs were divided into the following 3 groups: sham operation group (n = 6), 70% hepatectomy group (n = 7) as a safety margin of resection model, and 90% hepatectomy group (n = 7) as a liver failure model. Blood sampling was performed preoperatively and at 1, 6, 14, 30, 38, and 48 hours after surgery, and 129 primary metabolites were profiled. Orthogonal projection to latent structures-discriminant analysis revealed that, unlike in the 70% hepatectomy and sham operation groups, central carbon metabolism was the most significant factor in the 90% hepatectomy group. Binary logistic regression analysis was used to develop a predictive model for mortality risk following hepatectomy. the recommended variables were malic acid, methionine, tryptophan, glucose, and γ-aminobutyric acid. Area under the curve of the linear combination of five metabolites was 0.993 (95% confidence interval: 0.927-1.000, sensitivity: 100.0, specificity: 94.87). We proposed robust biomarker panels that can accurately predict mortality risk associated with hepatectomy. Liver resection is inevitable in the treatment of specific liver diseases. However, reduced liver volume can have many clinical manifestations such as small-for-size syndrome and post-hepatectomy liver failure, especially in cases of large volume resections of the liver. One of the main reasons for deteriorating liver function is high portal pressure, which results in high shear stress and sinusoidal injury 1. Conventional biochemical parameters for the evaluation of liver function in clinical settings, such as total bilirubin and prothrombin time (PT), are used as predictive markers. However, these biomarkers have limited usefulness in the prediction of early dysfunction. Total bilirubin and PT only have a 59% sensitivity in the prediction of postoperative mortality 2. Therefore, there is a need for more specific and accurate predictive markers. Metabolites are the final readouts of a range of endogenous biochemical activities. Changes in the metabolic profile are highly sensitive to internal and external challenges in biological systems. Thus, comprehensive metabolome information has great value in the diagnosis and prognosis of various diseases. In this study, we used liver failure animal models to determine changes in the levels of serum metabolites that can be identified before conventional biochemical markers. Two pig models were used to investigate the regenerating or failing liver after liver resection. Resection of 70% of the liver provided a model of liver injuries that did not lead to liver failure and served as a successful regenerative model, and resection of 90% of the liver provided a model of liver failure that eventually led to death. We identified ...

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“…While several metabolic pathways were reportedly downregulated in the liver following an AMI [ 12 ], we detected enrichment of genes implicated in the urea and tricarboxylic cycle (TCA) by the PBMCsec. Interestingly, the TCA cycle metabolites were decreased following hepatectomy with IR [ 63 ] and the AMI damage was ameliorated via enhancing TCA enzymatic activities [ 64 ]. Inducing TCA genes thus might seem a plausible mechanism by which the PBMCsec exerts distal hepato-protective effects after an AMI.…”

Section: Discussionmentioning

confidence: 99%

Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis

Mildner

Copic

Zimmermann

et al. 2022

Biology

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Acute myocardial infarction (AMI) is a result of cardiac non-perfusion and leads to cardiomyocyte necrosis, inflammation, and compromised cardiac performance. Here, we showed that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCsec) improved heart function in a porcine AMI model and displayed beneficial long- and short-term effects. As an AMI is known to strongly affect gene regulation of the ischemia non-affected heart muscle and distal organs, we employed a transcriptomics approach to further study the immediate molecular events orchestrated using the PBMCsec in myocardium, liver, and spleen 24 h post ischemia. In the infarcted area, the PBMCsec mainly induced genes that were essential for cardiomyocyte function and simultaneously downregulated pro-inflammatory genes. Interestingly, genes associated with pro-inflammatory processes were activated in the transition zone, while being downregulated in the remote zone. In the liver, we observed a pronounced inhibition of immune responses using the PBMCsec, while genes involved in urea and tricarboxylic cycles were induced. The spleen displayed elevated lipid metabolism and reduced immunological processes. Together, our study suggested several types of pharmacodynamics by which the PBMCsec conferred immediate cardioprotection. Furthermore, our data supported the assumption that an AMI significantly affects distal organs, suggesting that a holistic treatment of an AMI, as achieved by PBMCsec, might be highly beneficial.

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Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration

Cited by 11 publications

References 22 publications

Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis

Essential amino acids as diagnostic biomarkers of hepatocellular carcinoma based on metabolic analysis

Explorative study of serum biomarkers of liver failure after liver resection

Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis

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