N-Carbamoyl-l-Glutamate Plusl-Arginine Can Protect Ammonia Intoxication in Rats with Reduced Functional Liver Mass

Lee, Jae-Ho; Kim, Wook Hwan; Cho, Hyeseong; Kwak, Yun Sik; Kim, Sangduk; Paik, Woon Ki

doi:10.1006/bbrc.1998.8984

Cited by 5 publications

(6 citation statements)

References 15 publications

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“…Therefore, CG and Arg together might stimulate CPS I activity synergistically, thereby accelerating removal of ammonia through urea formation. In our previous study, pretreatment of the animals with CG plus Arg prior to the administration of a sub-lethal amount of ammonium acetate could indeed lower the blood ammonia level and change behavioral abnormality of 70% hepatectomized rats more efficiently than in the case of using either chemical alone [8].…”

Section: Discussionmentioning

confidence: 77%

“…For the control group, the same volume of PBS without the compounds was injected. Four hours later, a solution containing a sub-lethal dose of ammonium acetate (3.4 mmol/kg body weight in 1 ml PBS which was about one-third of LD99.9 [5,8]) was subcutaneously injected at the right side of the flank of both the control and test group rats. There was no difference between body weights of control and test group rats (data not shown).…”

Section: Treatment Of Compoundsmentioning

confidence: 99%

“…In the present study, we encountered a serious obstacle in administration of ammonium acetate and CG plus Arg, because of an unpredictable absorption due to ascites. Therefore, these compounds were subcutaneously given to cirrhotic rats, and the effect was much more delayed than intraperitoneal injection; therefore, CG plus Arg were injected 4 h before the ammonium acetate injection, instead of 1 h of intraperitoneal injection to non-cirrhotic rats [5,8].…”

Section: Experiments a (Time Course Of Blood Ammonia Level)mentioning

confidence: 99%

“…Apparently, the biosynthetic capacity of acetylglutamate synthetase appears to be limited and the level of N-acetyl-l-glutamate in mitochondria seems to be just barely sufficient to maintain an adequate level of activated CPS I. Since N-acetyl-l-glutamate is readily hydrolyzed in vivo, whereas its analogue CG is stable both in vivo and in vitro, we [5] earlier employed CG plus Arg to study the protective effect of these compounds on rats from intoxication by a lethal dose of ammonium acetate, and also recently demonstrated the ammonia-lowering effect of these compounds in rats whose liver mass was reduced by 70% after partial hepatectomy [8]. Since the largest ammonia-lowering effect was observed when two compounds were used together in the rat [5,8], the present study was designed to address whether the ammonia-lowering effect of the mixture can also be observed in cirrhotic conditions.…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Park

Yun

et al. 2001

Journal of Hepatology

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Section: Discussionmentioning

confidence: 77%

Section: Treatment Of Compoundsmentioning

confidence: 99%

Section: Experiments a (Time Course Of Blood Ammonia Level)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Kim

Park

Yun

et al. 2001

Journal of Hepatology

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“…B. beiK urzdarmsyndrom,mussauf eine ausreichende Argininzufuhr geachtetwerden.Andernfalls kommt es durcheinenMangelanOrnithin undei-nenA nstau vonC arbamylphosphat im Harnstoffzyklus zu einers ekundärenH yperammonämie. (16,19).…”

Section: Gastrointestinale Blutungenunclassified

Grundsätzliche und praktische Aspekte zur Hyperammonämie im Kindesalter

Häberle¹

2006

Kinder- und Jugendmedizin

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ZusammenfassungEine Hyperammonämie kann grundsätzlich in jedem Lebensalter auftreten und kann zu jedem Zeitpunkt lebensbedrohlich sein. Im Kindesalter liegt einer Hyperammonämie meist eine angeborene Stoffwechselkrankheit zugrunde.Klinisches Leitsymptom sind Appetitverlust und Bewusstseinsstörungen. Bei anhaltend hohen Ammoniakkonzentrationen droht die Entwicklung eines Hirnödems mit schlechter Prognose für Heilung oder überleben.Im Notfall ist die sofortige Einleitung von Diagnostik und Therapie entscheidend. Jede zeitliche Verzögerung kann für den Patienten fatale Folgen haben. Es muss sichergestellt sein, dass die Proben in ein spezialisiertes Labor versandt werden, in dem Diagnostik und Befundübermittlung innerhalb weniger Stunden gewährleistet sind.Es existieren diätetische und medikamentöse Möglichkeiten, den Stickstoffpool im Organismus zu reduzieren, um die ansonsten unausweichliche Neurotoxizität von Ammoniak zu verhindern. Als ultima ratio sind frühzeitig extrakorporale Verfahren der Gifteliminierung zu erwägen.

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Aberrations of ammonia metabolism in ornithine carbamoyltransferase-deficient spf-ash mice and their prevention by treatment with urea cycle intermediate amino acids and an ornithine aminotransferase inactivator

Nakajima

Fukushige

et al. 1999

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Sparse fur with abnormal skin and hair (spf-ash) mice are deficient in ornithine carbamoyltransferase (OCT) activity, but their OCT protein is kinetically normal. We administered ammonium chloride to spf-ash mice, in order to analyze ammonia metabolism and to find a rationale for the therapy of OCT deficiency. Ammonia concentration in the liver of spf-ash mice increased to a level much higher than in the control. Ammonium chloride injection caused an increase in ornithine (Orn) 5 min after injection and an increase in the sum of Orn, citrulline (Cit) and arginine (Arg) for at least 15 min in the liver of control mice, but no increase in Orn, Cit and Arg in the liver of spf-ash mice. Treatment of spf-ash mice with Arg 5-20 min prior to the injection of ammonium chloride kept the hepatic ammonia concentration at a level comparable to that without the load. A significant reciprocal relationship between ammonia and Orn concentrations in the liver of spf-ash mice 5 min after an ammonium chloride load with or without Arg strongly suggests that ammonia disposal is dependent on the supply of Orn. In spf-ash mice loaded with tryptone as a nitrogen source, Arg supplementation showed a dramatic decrease in urinary orotic acid excretion in a dose-dependent manner. Similar effects were observed with Cit and Orn at the same dose, and a long-lasting effect with an ornithine aminotransferase inactivator, 5-(fluoromethyl)ornithine, at a much lower dose. The rate of urea formation in liver perfused with ammonium chloride was lower in spf-ash mice than in controls, but with the addition of Orn to the medium it increased to a similar level in control and spf-ash mice. These results indicate that OCT is not saturated with Orn in vivo under physiological conditions and that the administration or enrichment of the urea cycle intermediate amino acids enhances the OCT reaction so that the ammonia metabolism of OCT-deficient spf-ash mice is at least partially normalized.

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N-Carbamoyl-l-Glutamate Plusl-Arginine Can Protect Ammonia Intoxication in Rats with Reduced Functional Liver Mass

Cited by 5 publications

References 15 publications

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

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

Grundsätzliche und praktische Aspekte zur Hyperammonämie im Kindesalter

Aberrations of ammonia metabolism in ornithine carbamoyltransferase-deficient spf-ash mice and their prevention by treatment with urea cycle intermediate amino acids and an ornithine aminotransferase inactivator

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