PMID- 35160278
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220219
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 11
IP  - 3
DP  - 2022 Feb 4
TI  - Is NMDA-Receptor-Mediated Oxidative Stress in Mitochondria of Peripheral Tissues 
      the Essential Factor in the Pathogenesis of Hepatic Encephalopathy?
LID - 10.3390/jcm11030827 [doi]
LID - 827
AB  - BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of 
      increased ammonia-mediated brain dysfunction caused by impaired hepatic 
      detoxification or when the blood bypasses the liver. Ammonia-activated signal 
      transduction pathways of hyperactivated NMDA receptors (NMDAR) are shown to 
      trigger a cascade of pathological reactions in the brain, leading to oxidative 
      stress. NMDARs outside the brain are widely distributed in peripheral tissues, 
      including the liver, heart, pancreas, and erythrocytes. To determine the 
      contribution of these receptors to ammonia-induced oxidative stress in peripheral 
      tissues, it is relevant to investigate if there are any ammonia-related changes 
      in antioxidant enzymes and free radical formation and whether blockade of NMDARs 
      prevents these changes. METHODS: Hyperammonemia was induced in rats by ammonium 
      acetate injection. Oxidative stress was measured as changes in antioxidant enzyme 
      activities and O(2)(*-) and H(2)O(2) production by mitochondria isolated from the 
      tissues and cells mentioned above. The effects of the NMDAR antagonist MK-801 on 
      oxidative stress markers and on tissue ammonia levels were evaluated. RESULTS: 
      Increased ammonia levels in erythrocytes and mitochondria isolated from the 
      liver, pancreas, and heart of hyperammonemic rats are shown to cause 
      tissue-specific oxidative stress, which is prevented completely (or partially in 
      erythrocyte) by MK-801. CONCLUSIONS: These results support the view that the 
      pathogenesis of HE is multifactorial and that ammonia-induced multiorgan 
      oxidative stress-mediated by activation of NMDAR is an integral part of the 
      disease and, therefore, the toxic effects of ammonia in HE may be more global 
      than initially expected.
FAU - Kosenko, Elena
AU  - Kosenko E
AUID- ORCID: 0000-0002-3293-652X
AD  - Institute of Theoretical and Experimental Biophysics of Russian Academy of 
      Sciences, 142290 Pushchino, Russia.
FAU - Tikhonova, Lyudmila
AU  - Tikhonova L
AUID- ORCID: 0000-0001-6310-0242
AD  - Institute of Theoretical and Experimental Biophysics of Russian Academy of 
      Sciences, 142290 Pushchino, Russia.
FAU - Alilova, Gubidat
AU  - Alilova G
AUID- ORCID: 0000-0001-8789-1712
AD  - Institute of Theoretical and Experimental Biophysics of Russian Academy of 
      Sciences, 142290 Pushchino, Russia.
FAU - Montoliu, Carmina
AU  - Montoliu C
AUID- ORCID: 0000-0002-4740-4788
AD  - Hospital Clinico Research Foundation, INCLIVA Health Research Institute, 46010 
      Valencia, Spain.
AD  - Pathology Department, Faculty of Medicine, University of Valencia, 46010 
      Valencia, Spain.
LA  - eng
GR  - numero sign 075-00381-21-00/ITEB RAS/
GR  - FIS PI18/00150/Ministerio de Ciencia e Innovacion Instituto de Salud Carlos III, 
      co-funded with European Regional Development Funds (ERDF), Fundacion Ramon 
      Areces/
PT  - Journal Article
DEP - 20220204
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC8836479
OTO - NOTNLM
OT  - NMDA receptors
OT  - antioxidant enzymes
OT  - erythrocytes
OT  - heart
OT  - hepatic encephalopathy
OT  - hydrogen peroxide
OT  - hyperammonemia
OT  - liver
OT  - mitochondria
OT  - oxidative stress
OT  - pancreas
OT  - superoxide radical
COIS- The authors declare no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2022/02/16 06:00
MHDA- 2022/02/16 06:01
PMCR- 2022/02/04
CRDT- 2022/02/15 01:07
PHST- 2021/12/20 00:00 [received]
PHST- 2022/02/01 00:00 [revised]
PHST- 2022/02/03 00:00 [accepted]
PHST- 2022/02/15 01:07 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/02/16 06:01 [medline]
PHST- 2022/02/04 00:00 [pmc-release]
AID - jcm11030827 [pii]
AID - jcm-11-00827 [pii]
AID - 10.3390/jcm11030827 [doi]
PST - epublish
SO  - J Clin Med. 2022 Feb 4;11(3):827. doi: 10.3390/jcm11030827.