Rat Model of Endogenous and Exogenous Hyperammonaemia Induced by Different Diets
Donaldson, Janine ; Jacek, Tomasz ; Wychowański, Piotr ; Zaworski, Kamil LU ; Szkopek, Dominika ; Woliński, Jarosław LU ; Grujic, Danica ; Pierzynowski, Stefan LU and Pierzynowska, Kateryna LU
(2025)
In International Journal of Molecular Sciences
26(5).
- Abstract
Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats,... (More)
Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies.
(Less)
- author
- Donaldson, Janine
; Jacek, Tomasz
; Wychowański, Piotr
; Zaworski, Kamil
LU
; Szkopek, Dominika
; Woliński, Jarosław
LU
; Grujic, Danica
; Pierzynowski, Stefan
LU
and Pierzynowska, Kateryna
LU
- organization
- publishing date
- 2025-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ammonium acetate, dietary hyperammonaemia, hepatic encephalopathy, methionine–choline-deficient diet, rat model
- in
- International Journal of Molecular Sciences
- volume
- 26
- issue
- 5
- article number
- 1818
- publisher
- MDPI AG
- external identifiers
-
- pmid:40076444
- scopus:86000598087
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms26051818
- language
- English
- LU publication?
- yes
- id
- 3546654e-740c-4e8e-9aba-97a02350930e
- date added to LUP
- 2025-06-24 10:54:02
- date last changed
- 2025-06-25 03:00:09
@article{3546654e-740c-4e8e-9aba-97a02350930e,
abstract = {{<p>Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies.</p>}},
author = {{Donaldson, Janine and Jacek, Tomasz and Wychowański, Piotr and Zaworski, Kamil and Szkopek, Dominika and Woliński, Jarosław and Grujic, Danica and Pierzynowski, Stefan and Pierzynowska, Kateryna}},
issn = {{1661-6596}},
keywords = {{ammonium acetate; dietary hyperammonaemia; hepatic encephalopathy; methionine–choline-deficient diet; rat model}},
language = {{eng}},
number = {{5}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{Rat Model of Endogenous and Exogenous Hyperammonaemia Induced by Different Diets}},
url = {{http://dx.doi.org/10.3390/ijms26051818}},
doi = {{10.3390/ijms26051818}},
volume = {{26}},
year = {{2025}},
}