A Study of the Metabolites of Ischemia-Reperfusion Injury and Selected Amino Acids in the Liver Using Microdialysis during Transplantation

Silva, Michael A.; Richards, Douglas A.; Bramhall, Simon R.; Adams, David H.; Mirza, Darius F.; Murphy, Nick

doi:10.1097/01.tp.0000153156.38617.97

Cited by 59 publications

(50 citation statements)

References 38 publications

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“…Recently, most metabolomic studies were focused on kidney transplantation to assess biomarkers associated with posttransplantation function, renal dysfunction, acute rejection and subclinical rejection [1,9,10,11,12,13,14,15,16,17] and others on liver and heart transplantation [18,19,20,21] to identify prognostic and diagnostic markers of organ rejection and dysfunction [22,23,24]. This is the first time that the metabonomics technique has been applied to human intestinal transplantation.…”

Section: Discussionmentioning

confidence: 99%

Metabonomics Study of Intestinal Transplantation Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry

Qiang

et al. 2008

Digestion

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Background: Intestinal transplantation is a potential treatment for patients with irreversible intestinal failure. However, the long-term outcome is still unsatisfactory compared with transplantation of other solid organs because of transplantation rejection. Therefore, early detection and accurate diagnosis of rejection is essential. Recently, metabonomics has become a platform for monitoring of the process of organ transplantation. Methods: The metabolite profiling in the plasma was measured by ultrahigh-performance liquid chromatography time-of-flight mass spectrometry in a patient with intestinal transplantation and it was analyzed by principal component analysis and SIMCA-P. Results: The differences between the patient and controls were achieved in the principal component analysis score plot. The potential biomarkers of rejection, including lysophosphatidyl choline, phenylalanine and tryptophan, were identified in the transplantation patient. Conclusion: The analysis here may provide a fundamental and powerful approach to inspect the disease metabolic status and screening tool for marker candidates.

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Section: Discussionmentioning

confidence: 99%

Metabonomics Study of Intestinal Transplantation Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry

Qiang

et al. 2008

Digestion

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“…In 2003, Singh et al [10] developed an NMR method in order to assess liver graft dysfunction. Silva et al [11] have shown a way to measure the extent of organ injury due to storage before surgery using NMR. Another approach to find metabolic biomarkers was reported by Duarte et al by analysing biopsy samples from livers before and after the transplantation.…”

Section: Introductionmentioning

confidence: 99%

Fingerprinting of human bile during liver transplantation by capillary electrophoresis

Papaspyridonos¹,

García-Pérez²,

Angulo³

et al. 2008

J of Separation Science

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Increasing rates of success in liver transplantation have increased the number of cases considered. However, liver post-transplant graft dysfunction of liver transplants (TXs) is not fully understood and by applying holistic approaches we can investigate metabolic change deriving from confounding factors such as liver fat content, ischaemia time, donor age, recipient's health, etc. Twenty-six hepatic bile samples taken from liver donors and recipients were retrieved from a total of six TXs, from these one recipient underwent post-graft dysfunction. CE was employed to fingerprint bile collected at 10 min increments in the donors and in the recipients. The electropherograms of these samples were aligned and normalised using correlation optimised warping algorithms and modelled with multivariate techniques. The resulting metabolic signatures were compared; in general donors and recipients showed distinct fingerprints and clustered separately. When a partial least square discriminant analysis (PLS-DA) model was constructed between donor and recipient's samples, a recipient of a 32 year old liver with normal steatosis, and shortest cold ischaemia time showed as the observation nearest to its donor observation, denoting minimal metabolic change. This study proposes CE fingerprinting of human bile as a promising technique to help unravel the complex metabolic pathways involved during transplantation.

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“…As a consequence, blockade of LPS-induced KC activation with glycine, has been shown to reduce hepatic I/RI in animal models and humans [8][9][10][11] . Glycine is a nontoxic nonessential amino acid and inhibitory neurotransmitter in the central nervous system [12] .…”

Section: Introductionmentioning

confidence: 99%

Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

Liu

Yan

et al. 2006

Acta Pharmacologica Sinica

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Aim: To determine whether glycine could downregulate interleukin 1 receptor associated kinase-4 (IRAK-4) expression to interfere with lipopolysaccharides (LPS) signal transduction and blunt transplantative liver ischemia-reperfusion injury (I/RI). Methods: SD rats were randomly divided into two groups: donor animals of the glycine group (n=40) were given glycine (1.5 mL; 300 mmol/L, iv) 1 h before harvest, and the control group were treated with 1.5 mL physiological saline (n= 40). Orthotropic liver transplantation was then performed according to the Kamada technique. Ten animals in each group were followed up for 7 d after surgery to assess survival. The remaining animals in each group were divided into 3 subgroups (n=10) at 1h, 2 h and 6 h after portal vein reperfusion. Levels of LPS, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin in portal circulation, as well as IRAK-4 and TNF-α expression, NF-κB transcriptional activity and morphological study of liver tissues were analyzed. Results: Reperfusion resulted in a significant elevation of LPS concentrations in each group persisting to the end of our study. However, glycine, which led to improved survival rate and liver function, significantly alleviated liver parenchyma cell damage by downregulating IRAK-4, TNF-α expression and NF-κB transcriptional activity compared with the control group. Conclusion: Glycine can attenuate hepatic I/RI by downregulating IRAK-4 to interfere with LPS signal transduction.

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A Study of the Metabolites of Ischemia-Reperfusion Injury and Selected Amino Acids in the Liver Using Microdialysis during Transplantation

Cited by 59 publications

References 38 publications

Metabonomics Study of Intestinal Transplantation Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry

Metabonomics Study of Intestinal Transplantation Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry

Fingerprinting of human bile during liver transplantation by capillary electrophoresis

Glycine blunts transplantative liver ischemia-reperfusion injury by downregulating interleukin 1 receptor associated kinase-4

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