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N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice
AIM OF THE STUDY: Acute or chronic live failure could result in hyperammonemia and hepatic encephalopathy (HE). HE is a clinical complication characterized by severe cognitive dysfunction and coma. The ammonium ion (NH(4)(+)) is the most suspected toxic molecule involved in the pathogenesis of HE. N...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Termedia Publishing House
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380475/ https://www.ncbi.nlm.nih.gov/pubmed/32728627 http://dx.doi.org/10.5114/ceh.2020.95814 |
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author | Mohammadi, Hamidreza Sayad, Abolfazl Mohammadi, Mohsen Niknahad, Hossein Heidari, Reza |
author_facet | Mohammadi, Hamidreza Sayad, Abolfazl Mohammadi, Mohsen Niknahad, Hossein Heidari, Reza |
author_sort | Mohammadi, Hamidreza |
collection | PubMed |
description | AIM OF THE STUDY: Acute or chronic live failure could result in hyperammonemia and hepatic encephalopathy (HE). HE is a clinical complication characterized by severe cognitive dysfunction and coma. The ammonium ion (NH(4)(+)) is the most suspected toxic molecule involved in the pathogenesis of HE. NH(4)(+) is a neurotoxic agent. Different mechanisms, including oxidative/nitrosative stress, inflammatory response, excitotoxicity, and mitochondrial impairment, are proposed for NH(4)(+)-induced neurotoxicity. N-acetyl cysteine (NAC) is a well-known thiol-reductant and antioxidant agent. Several investigations also mentioned the positive effects of NAC on mitochondrial function. In the current study, the effect of NAC treatment on brain mitochondrial indices and energy status was investigated in an animal model of HE. MATERIAL AND METHODS: Acetaminophen (APAP)-induced acute liver failure was induced by a single dose of the drug (800 mg/kg, i.p.) to C57BL/6J mice. Plasma and brain levels of NH(4)(+) were measured. Then, brain mitochondria were isolated, and several indices, including mitochondrial depolarization, ATP level, lipid peroxidation, glutathione content, mitochondrial permeabilization, and dehydrogenase activity, were assessed. RESULTS: A significant increase in plasma and brain NH(4)(+) was evident in APAP-treated animals. Moreover, mitochondrial indices of functionality were impaired, and mitochondrial oxidative stress biomarkers were significantly increased in APAP-treated mice. It was found that NAC treatment (100, 200, and 400 mg/kg, i.p.) significantly mitigated mitochondrial impairment in the brain of APAP-treated animals. CONCLUSIONS: These data suggest the effects of NAC on brain mitochondrial function and energy status as a pivotal mechanism involved in its neuroprotective properties during HE. |
format | Online Article Text |
id | pubmed-7380475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Termedia Publishing House |
record_format | MEDLINE/PubMed |
spelling | pubmed-73804752020-07-28 N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice Mohammadi, Hamidreza Sayad, Abolfazl Mohammadi, Mohsen Niknahad, Hossein Heidari, Reza Clin Exp Hepatol Original Paper AIM OF THE STUDY: Acute or chronic live failure could result in hyperammonemia and hepatic encephalopathy (HE). HE is a clinical complication characterized by severe cognitive dysfunction and coma. The ammonium ion (NH(4)(+)) is the most suspected toxic molecule involved in the pathogenesis of HE. NH(4)(+) is a neurotoxic agent. Different mechanisms, including oxidative/nitrosative stress, inflammatory response, excitotoxicity, and mitochondrial impairment, are proposed for NH(4)(+)-induced neurotoxicity. N-acetyl cysteine (NAC) is a well-known thiol-reductant and antioxidant agent. Several investigations also mentioned the positive effects of NAC on mitochondrial function. In the current study, the effect of NAC treatment on brain mitochondrial indices and energy status was investigated in an animal model of HE. MATERIAL AND METHODS: Acetaminophen (APAP)-induced acute liver failure was induced by a single dose of the drug (800 mg/kg, i.p.) to C57BL/6J mice. Plasma and brain levels of NH(4)(+) were measured. Then, brain mitochondria were isolated, and several indices, including mitochondrial depolarization, ATP level, lipid peroxidation, glutathione content, mitochondrial permeabilization, and dehydrogenase activity, were assessed. RESULTS: A significant increase in plasma and brain NH(4)(+) was evident in APAP-treated animals. Moreover, mitochondrial indices of functionality were impaired, and mitochondrial oxidative stress biomarkers were significantly increased in APAP-treated mice. It was found that NAC treatment (100, 200, and 400 mg/kg, i.p.) significantly mitigated mitochondrial impairment in the brain of APAP-treated animals. CONCLUSIONS: These data suggest the effects of NAC on brain mitochondrial function and energy status as a pivotal mechanism involved in its neuroprotective properties during HE. Termedia Publishing House 2020-05-30 2020-06 /pmc/articles/PMC7380475/ /pubmed/32728627 http://dx.doi.org/10.5114/ceh.2020.95814 Text en Copyright © 2020 Clinical and Experimental Hepatology http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/) |
spellingShingle | Original Paper Mohammadi, Hamidreza Sayad, Abolfazl Mohammadi, Mohsen Niknahad, Hossein Heidari, Reza N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title | N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title_full | N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title_fullStr | N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title_full_unstemmed | N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title_short | N-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
title_sort | n-acetyl cysteine treatment preserves mitochondrial indices of functionality in the brain of hyperammonemic mice |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380475/ https://www.ncbi.nlm.nih.gov/pubmed/32728627 http://dx.doi.org/10.5114/ceh.2020.95814 |
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