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Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: comparison of the enzymes’ response to in vitro treatment with ammonia

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Abstract

Hepatic encephalopathy can be a life-threatening complication of fulminant hepatic failure. By understanding the pathophysiology involved in the induction of this neuropsychiatric disorder, future therapeutic and/or preventive attempts could be considered. In this study, an attempt has been made in order to shed more light on the mechanisms involved in the effects of thioacetamide (TAA)-induced fulminant hepatic encephalopathy on: (a) the adult rat brain total antioxidant status (TAS) and (b) the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+-ATPase. Moreover, in vitro experiments were conducted in order to evaluate the possible role of ammonia (incubated as NH4Cl, in a toxic concentration of 3mM) in the observed effects of TAA-induced fulminant hepatic encephalopathy on the examined adult rat brain enzyme activities. Fulminant hepatic encephalopathy caused a significant decrease in TAS (−22%, p < 0.001) and the activity of Na+,K+-ATPase (−26%, p < 0.001), but had non-significant effects on the whole brain AChE and Mg2+-ATPase activities. The in vitro experiments (conducted through a 3h incubation with ammonia), showed no significant alterations in any of the examined parameters. Our in vitro and in vivo findings suggest that alterations in AChE and Mg2+-ATPase activities are not involved in the pathophysiology of the adult-onset fulminant hepatic encephalopathy, while the observed Na+,K+-ATPase inhibition could be a result of the oxidative stress, neurotransmission deregulation, and/or of the presence of other toxic substances (that appear to act as direct or indirect inhibitors of the enzyme) and not due to the excess accumulation of ammonia in the brain.

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Acknowledgements

This work was funded by the University of Athens. The authors wish to acknowledge their appreciation to the medical students Marios Margaritis and Anastasios Pantazopoulos for their assistance.

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Authors and Affiliations

  1. Department of Physiology, Medical School, University of Athens, P.O. Box 65257, Athens, Greece

    Apostolos Zarros, Nikolina Skandali & Stylianos Tsakiris

  2. Department of Forensic Medicine and Toxicology, Medical School, University of Athens, Athens, Greece

    Stamatios Theocharis

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  1. Apostolos Zarros
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  2. Stamatios Theocharis
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  3. Nikolina Skandali
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  4. Stylianos Tsakiris
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Correspondence to Stylianos Tsakiris.

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Zarros, A., Theocharis, S., Skandali, N. et al. Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: comparison of the enzymes’ response to in vitro treatment with ammonia. Metab Brain Dis 23, 255–264 (2008). https://doi.org/10.1007/s11011-008-9091-8

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