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Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats

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Abstract

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [13N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [13N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [13N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2–10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.

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Abbreviations

BBB:

Blood–brain barrier

BUI:

Brain uptake index

HE:

Hepatic encephalopathy

PCS:

Portacaval shunt

PET:

Positron-emission tomography

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Acknowledgements

We thank Dr. Barry Freed for his contributions to the synthesis of 13N and the labeling experiments.

Funding

This work was supported by National Institutes of Health Grants DK 16739 and DK 37116.

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Authors and Affiliations

  1. Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Nancy F. Cruz & Gerald A. Dienel

  2. Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, USA

    Gerald A. Dienel

  3. Westchester Institute for Human Development, Valhalla, NY, USA

    Patricia A. Patrick

  4. Department of Biochemistry and Molecular Biology, New York Medical College, 15 Dana Road, Valhalla, NY, 10595, USA

    Arthur J. L. Cooper

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  1. Nancy F. Cruz
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  2. Gerald A. Dienel
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  4. Arthur J. L. Cooper
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Correspondence to Arthur J. L. Cooper.

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Cruz, N.F., Dienel, G.A., Patrick, P.A. et al. Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats. Neurochem Res 42, 1683–1696 (2017). https://doi.org/10.1007/s11064-016-2096-5

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