Mixture of N-carbamoyl-l-glutamate plus l-arginine can protect rats with liver cirrhosis from acute ammonia intoxication

Kim, Wook Hwan; Park, Hyelee; Yun, Chawon; Cho, Hyeseong; Kim, Sangduk; Paik, Woon Ki; Jeon, Soung Hoo; Lee, Jae Ho

doi:10.1016/s0168-8278(01)00199-4

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…For example, the administration of Arg reduces damage to liver tissue after ischaemia injury [13]. In addition, it has been reported that Arg could protect rats with liver cirrhosis from acute ammonia intoxication [28]. …”

Section: Discussionmentioning

confidence: 99%

Effect of L-arginine on HSP70 expression in liver in weanling piglets

Xie

Yin

et al. 2013

BMC Vet Res

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BackgroundThis study was conducted to evaluate the effects of L-arginine (Arg) on photomicrographs and HSP70 expression in the liver of weanling piglets. Twelve healthy Landrace × Yorkshire piglets that had been weaned at 21 d (average body weight 5.56 ± 0.51 kg) were randomly divided into a control group and an Arg group (6 g/kg feed). At age 28 d, all of the piglets were slaughtered to obtain liver samples to determine HSP70 expression by real-time PCR, western blot and immunohistochemistry.ResultsThe results showed that, compared to control piglets, treatment with Arg decreased inflammatory reactions caused by weaning. The immunohistochemical localization of HSP70 in liver revealed strong expression in the Arg group. Arg increased HSP70 mRNA and HSP70 expression in the liver (P < 0.05).ConclusionsThese findings suggest that dietary supplementation with Arg could maintain liver health by inducing HSP70 expression in weanling piglets.

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Section: Discussionmentioning

confidence: 99%

Effect of L-arginine on HSP70 expression in liver in weanling piglets

Xie

Yin

et al. 2013

BMC Vet Res

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“…It has been further reported that the activity of ATA2 (20,21) is adaptively up-regulated in response to physiological changes such as nutrient starvation. Since the cellular requirements for amino acids including L-arginine are increased during liver cirrhosis and fibrosis (22)(23)(24), the elevation of AT mRNAs in precancerous livers may thus also be attributable to nutrient starvation.…”

Section: Discussionmentioning

confidence: 99%

Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues

Kondoh

Imazeki²,

Arai³

et al. 2007

Int J Oncol

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Abstract. The expression of amino acid transporter (AT) mRNAs including A system (ATA1/SNAT1/SLC38A1, ATA2/ SNAT2/SLC38A2 and ATA3/SNAT3/SLC38A4), L system (LAT1/SLC7A5 and LAT2/SLC7A8), and y + (CAT2/SLC7A2) genes, were compared among hepatocellular carcinoma (HCC) and non-cancerous liver cells. Among them the ATA1 mRNA expression was significantly elevated in all HCC cell lines (HepG2, HLF, HuH7 and JHH4) examined compared with normal liver tissue. We further discovered that the expression of ATA1 mRNA was significantly activated in HCC tissues and also elevated in pre-malignant cirrhotic livers from HCC patients, compared with normal livers from non-HCC patients. The ATA1 protein was extensively accumulated in the cytoplasm of pre-malignant liver and most HCCs, while being weak or undetectably low in normal liver tissues. SiRNAmediated suppression of endogenous ATA1 lowered the viability of HepG2 cells. Thus, the activation of ATA1 confers growth and survival advantages in pre-malignant and malignant liver lesions.

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“…NCG has been proven to be safe in all age groups and represents a life-changing treatment in the management of NAGS deficiency. Future studies are necessary to validate its use for other IEM or conditions such as hepatic encephalopathy as proposed by the studies in healthy human subjects and a rat cirrhotic model [8,73]. In general, hyperammonemia caused by conditions other than defects in the urea cycle are complex with involvement of multiple factors and the contribution of secondary NAGS deficiency may be fractional.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of N-carbamoyl-L-glutamic acid for the treatment of inherited metabolic disorders

Chapel-Crespo

Diaz

Oishi

2016

Expert Review of Endocrinology & Metabolism

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Introduction N-carbamoyl-L-glutamic acid (NCG) is a synthetic analogue of N-acetyl glutamate (NAG) that works effectively as a cofactor for carbamoyl phosphate synthase 1 and enhances ureagenesis by activating the urea cycle. NCG (brand name, Carbaglu) was recently approved by the United States Food and Drug Administration (US FDA) for the management of NAGS deficiency and by the European Medicines Agency (EMA) for the treatment of NAGS deficiency as well as for the treatment of hyperammonenia in propionic, methylmalonic and isovaleric acidemias in Europe. Areas covered The history, mechanism of action, and efficacy of this new drug are described. Moreover, clinical utility of NCG in a variety of inborn errors of metabolism with secondary NAGS deficiency is discussed. Expert commentary NCG has favorable pharmacological features including better bioavailability compared to NAG. The clinical use of NCG has proven to be so effective as to make dietary protein restriction unnecessary for patients with NAGS deficiency. It has been also demonstrated to be effective for hyperammonemia secondary to other types of inborn errors of metabolism. NCG may have additional therapeutic potential in conditions such as hepatic hyperammonemic encephalopathy secondary to chemotherapies or other liver pathology.

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Mixture of N-carbamoyl-l-glutamate plus l-arginine can protect rats with liver cirrhosis from acute ammonia intoxication

Cited by 6 publications

References 21 publications

Effect of L-arginine on HSP70 expression in liver in weanling piglets

Effect of L-arginine on HSP70 expression in liver in weanling piglets

Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues

Efficacy of N-carbamoyl-L-glutamic acid for the treatment of inherited metabolic disorders

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