A gas, an amino acid, and an imposter

Langer, Daniël; Shah, Vijay H.

doi:10.1002/hep.20989

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…In addition to bile acids, several metabolites that are part of the aromatic amino acid, arginine and benzoate metabolism were significantly associated with the development of ACLF and death. The arginine metabolites ADMA and SDMA, which adversely impact vascular reactivity and brain function, were higher in patients who developed poor outcomes compared to those who did not 42,43 . Tryptophan metabolites have the potential to engage the aryl-hydrocarbon (AhR) receptor and can cause several downstream positive effects on the systemic circulation, brain and liver 34,44 .…”

Section: Discussionmentioning

confidence: 89%

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis

et al. 2020

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Section: Discussionmentioning

confidence: 89%

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis

et al. 2020

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“…ADMA is considered to be an end-product of nitric oxide that can result in reverse inhibition and a false-transmitter[11]. While this role can associate ADMA with endothelial dysfunction and poor cardiovascular outcomes in patients without liver disease, its role in cirrhosis is complicated by the localization of DDAH in the liver[17, 18].…”

Section: Discussionmentioning

confidence: 99%

“…Asymmetric di-methyl arginine (ADMA) is a by-product of amino acid metabolism that can interfere with nitric oxide synthesis by competitive inhibition of endothelial nitric oxide synthase (eNOS)[11]. Increased levels of ADMA are associated with endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric dimethylarginine is strongly associated with cognitive dysfunction and brain MR spectroscopic abnormalities in cirrhosis

Bajaj

Ahluwalia

Wade

et al. 2013

Journal of Hepatology

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Background Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that accumulates in liver disease and may contribute to hepatic encephalopathy(HE). Aim To evaluate the association of ADMA with cognition and brain MR spectroscopy(MRS) in cirrhosis. Methods Cirrhotic patients with/without prior HE and non-cirrhotic controls underwent cognitive testing and ADMA determination. A subgroup underwent brain MRS [Glutamine/glutamate(Glx), myoinositol(mI), N-acetyl-aspartate(NAA) in parietal white, occipital gray and anterior cingulate(ACC)]. We also tested cognition and ADMA in a cirrhotic subgroup before and 1 month after transjugular intrahepatic portosystemic shunting (TIPS). Cognition and MRS values were correlated with ADMA and compared between groups using multi-variable regression. ADMA levels were compared between those who did/did not develop post-TIPS HE. Results 90 cirrhotics (MELD13, 54 prior HE) and 16 controls were included. Controls had better cognition and lower ADMA, Glx and higher mI compared to cirrhotics. Prior HE patients had worse cognition, higher ADMA and Glx and lower mI compared to non-HE cirrhotics. ADMA was positively correlated with MELD (r=0.58,p<0.0001), abnormal cognitive test number(r=0.66,p<0.0001) and Glx and NAAA (white matter,ACC) and negatively with mI. On regression, ADMA predicted number of abnormal tests and mean Z-score independent of prior HE and MELD. 12 patients underwent TIPS;7 developed HE post-TIPS. ADMA increased post-TIPS in patients who developed HE(p=0.019) but not in others(p=0.89). Conclusions A strong association of ADMA with cognition and prior HE was found independent of MELD score in cirrhosis.

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“…Nitric oxide (NO), synthetized from arginine (ARG), is an essential factor regulating relaxation and dilatation of hepatic stellate cells, and hence, sinusoid blood flow. [1][2][3] Endothelial NO synthase (eNOS) is responsible for both the basal production of NO and, when larger amounts of NO are required, the production for its inducible form -iNOS. At a higher concentration, NO reacts with superoxide, forming peroxinitrite, which augments cell injury.…”

Section: Introductionmentioning

confidence: 99%

The impact of sitagliptin, inhibitor of dipeptidyl peptidase-4 (DPP-4), on the ADMA-DDAH-NO pathway in ischemic and reperfused rat livers

Trocha¹,

Nowak²,

Merwid-Ląd³

et al. 2018

Adv Clin Exp Med

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Background. A correlation between the level of asymmetric dimethylarginine (ADMA)-the inhibitor of the nitric oxide (NO) synthesis-and the liver function and survival after a liver transplantation has been reported. Objectives. The aim of this study was to evaluate the effect of sitagliptin-the inhibitor of dipeptidyl peptidase-4 (DPP-4)-on the NO-ADMA-dimethylarginine dimethylaminohydrolase (DDAH) pathway in rat livers subjected to ischemia/reperfusion (IR). Material and methods. The rats received sitagliptin (5 mg/kg, per os-p.o.) (groups: Slivers not subjected to IR procedure, and SIR-livers subjected to IR procedure) or a saline solution (groups: C-livers not subjected to IR procedure, and CIR-livers subjected to IR procedure) for 14 days; following this, livers in the SIR and CIR groups were subjected to ischemia (60 min) and reperfusion (24 h). Aminotransferases were measured before the surgery; additionally, the arginine (ARG), ADMA and symmetric dimethylarginine (SDMA) levels were estimated just before ischemia and during reperfusion (at 0.5 h, 4 h and 24 h). After IR, citrulline, the DDAH activity, mRNA for type 1 DDAH (DDAH1), and arginine methyltransferase type 1 (PRMT1) were determined. Results. The increase in the initial level of ARG/ADMA0 (A/A) ratio in group S compared to group C verged on statistical significance. At 0.5 h and 4 h of reperfusion, the highest concentration of ADMA was found in group CIR. At those time points, the ARG level and the A/A ratio were decreased in groups CIR and SIR as compared to groups C and S, respectively. The alanine transaminase (ALT) activity was lower in the sitagliptintreated group than in the non-treated one. The DDAH and citrulline levels were reduced in group CIR as compared to group C, but were greater in group SIR as compared to group S. The PRMT1 mRNA expression was higher in groups CIR and SIR, compared to groups C and S, respectively. Conclusions. The increased A/A ratio suggests a protective effect of sitagliptin on livers not subjected to IR. Changes in the DDAH activity and the PRMT1 mRNA expression also imply the protective activity of sitagliptin during IR.

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A gas, an amino acid, and an imposter

Cited by 5 publications

References 26 publications

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis

Serum Levels of Metabolites Produced by Intestinal Microbes and Lipid Moieties Independently Associated With Acute-on-Chronic Liver Failure and Death in Patients With Cirrhosis

Asymmetric dimethylarginine is strongly associated with cognitive dysfunction and brain MR spectroscopic abnormalities in cirrhosis

The impact of sitagliptin, inhibitor of dipeptidyl peptidase-4 (DPP-4), on the ADMA-DDAH-NO pathway in ischemic and reperfused rat livers

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