Dipeptiven® is safe in a rat model of moderate liver dysfunction
Summary: Background & aims: Administration of glutamine in patients with liver failure is thought to possibly increase blood ammonia levels, thereby contributing to hepatic encephalopathy. In a rat model of moderate liver dysfunction with elevated plasma glutamine concentrations dose-dependent...
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2018-10-01
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Series: | Clinical Nutrition Experimental |
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doaj-1e69b765751b4b95bb796d60bf3643c12020-11-25T02:25:50ZengElsevierClinical Nutrition Experimental2352-93932018-10-0121917Dipeptiven® is safe in a rat model of moderate liver dysfunctionMelanie K. Bothe0Rosa Abele1Heinrich Topp2Johannes Harleman3Martin Westphal4John F. Stover5Corresponding author.; Fresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanyFresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanyFresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanyFresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanyFresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanyFresenius Kabi Deutschland GmbH, Else-Kröner-Strasse 1, 61352 Bad Homburg, GermanySummary: Background & aims: Administration of glutamine in patients with liver failure is thought to possibly increase blood ammonia levels, thereby contributing to hepatic encephalopathy. In a rat model of moderate liver dysfunction with elevated plasma glutamine concentrations dose-dependent effects of intravenous alanyl-glutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods: Rats with moderate liver dysfunction resulting from alpha-naphthylisothiocyanate (ANIT) induced cholestasis received a 9 days continuous intravenous infusion of 0.5 g/kg/day or 3.0 g/kg/day alanyl-glutamine (Dipeptiven®). Dose-dependent effects on liver injury were assessed by analyzing blood levels of ammonia, urea, ALT, AST, and ALP, glutamine, and histopathology. Results: Continuous intravenous infusion of 3.0 g/kg/day alanyl-glutamine increased plasma glutamine concentrations up to 30% without increasing blood ammonia levels or inducing astrocyte swelling. Alanyl-glutamine did not aggravate underlying liver injury shown by absent increase in plasma levels of ALT, AST, ALP and no signs of histopathologic alterations. Conclusions: Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat model of moderate liver dysfunction based on ANIT-induced cholestasis. Keywords: Ammonia, Astrocyte swelling, Brain edema, Cholestasis, Glutamine, Liver injuryhttp://www.sciencedirect.com/science/article/pii/S2352939318300216 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Melanie K. Bothe Rosa Abele Heinrich Topp Johannes Harleman Martin Westphal John F. Stover |
spellingShingle |
Melanie K. Bothe Rosa Abele Heinrich Topp Johannes Harleman Martin Westphal John F. Stover Dipeptiven® is safe in a rat model of moderate liver dysfunction Clinical Nutrition Experimental |
author_facet |
Melanie K. Bothe Rosa Abele Heinrich Topp Johannes Harleman Martin Westphal John F. Stover |
author_sort |
Melanie K. Bothe |
title |
Dipeptiven® is safe in a rat model of moderate liver dysfunction |
title_short |
Dipeptiven® is safe in a rat model of moderate liver dysfunction |
title_full |
Dipeptiven® is safe in a rat model of moderate liver dysfunction |
title_fullStr |
Dipeptiven® is safe in a rat model of moderate liver dysfunction |
title_full_unstemmed |
Dipeptiven® is safe in a rat model of moderate liver dysfunction |
title_sort |
dipeptiven® is safe in a rat model of moderate liver dysfunction |
publisher |
Elsevier |
series |
Clinical Nutrition Experimental |
issn |
2352-9393 |
publishDate |
2018-10-01 |
description |
Summary: Background & aims: Administration of glutamine in patients with liver failure is thought to possibly increase blood ammonia levels, thereby contributing to hepatic encephalopathy. In a rat model of moderate liver dysfunction with elevated plasma glutamine concentrations dose-dependent effects of intravenous alanyl-glutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods: Rats with moderate liver dysfunction resulting from alpha-naphthylisothiocyanate (ANIT) induced cholestasis received a 9 days continuous intravenous infusion of 0.5 g/kg/day or 3.0 g/kg/day alanyl-glutamine (Dipeptiven®). Dose-dependent effects on liver injury were assessed by analyzing blood levels of ammonia, urea, ALT, AST, and ALP, glutamine, and histopathology. Results: Continuous intravenous infusion of 3.0 g/kg/day alanyl-glutamine increased plasma glutamine concentrations up to 30% without increasing blood ammonia levels or inducing astrocyte swelling. Alanyl-glutamine did not aggravate underlying liver injury shown by absent increase in plasma levels of ALT, AST, ALP and no signs of histopathologic alterations. Conclusions: Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat model of moderate liver dysfunction based on ANIT-induced cholestasis. Keywords: Ammonia, Astrocyte swelling, Brain edema, Cholestasis, Glutamine, Liver injury |
url |
http://www.sciencedirect.com/science/article/pii/S2352939318300216 |
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