Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na(+),K (+))- and Mg (2+)-ATPase: comparison of the enzymes' response to in vitro treatment with ammonia.

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 Mg(2+)-ATPase. Moreover, in vitro experiments were conducted in order to evaluate the possible role of ammonia (incubated as NH(4)Cl, 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 Mg(2+)-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 Mg(2+)-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.

journal_name

Metab Brain Dis

journal_title

Metabolic brain disease

authors

Zarros A,Theocharis S,Skandali N,Tsakiris S

doi

10.1007/s11011-008-9091-8

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

255-64

issue

3

eissn

0885-7490

issn

1573-7365

journal_volume

23

pub_type

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