Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy: Possible mechanisms of neurotoxic effects

D Mladenovic,Olivera Stanojlovic,A Rasic-Markovic,D Hrncic

doi:10.2298/abs1203829m

D Mladenovic, Olivera Stanojlovic + Show 2 more

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https://doi.org/10.2298/abs1203829m

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Abstract

Although there is still no ideal experimental model of hepatic encephalopathy, thioacetamide is widely used for the induction of acute and chronic liver failure. Thioacetamide exerts hepatotoxic effects through the formation of toxic metabolites in hepatocytes, oxidative stress and calcium mobilization. An ideal experimental model of hepatic encephalopathy should have similar behavioral and electroencephalographic manifestations as human encephalopathy. Thioacetamide induces motor manifestations in a dose-dependent manner. Milder forms of thioacetamide-induced encephalopathy are associated with an increase in relative alpha power, while more severe forms are followed by a flattening of the electroencephalogram. liver failure-induced hyperammonemia has a pivotal role in the neurotoxic effects of thioacetamide. Hyperammonemia induces brain edema, alterations in neurotransmission, oxidative stress, mitochondrial dysfunction and neuronal death. The aim of this article is to review the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy, as well as to summarize potential mechanisms involved in thioacetamide neurotoxicity.

Highlights

Thioacetamide (TAA) is a sulfur-containing compound that may be used in agriculture, as well as in rubber and paper industries and metallurgy
The aim of this review is to summarize the behavioral and electroencephalographic manifestations of TAA-induced encephalopathy, to compare them with manifestations of human hepatic encephalopathy (HE), as well as to describe potential mechanisms involved in the pathogenesis of this encephalopathy
Sabra mice were found to be even more sensitive to the neurotoxic effects of TAA, since a dose of 200 mg/kg of TAA induced encephalopathy in this mice strain (Avraham et al, 2006). These findings indicate that TAA in an appropriate dose may be used for the induction of the behavioral manifestations of acute liver failure in mice and rats

Summary

Introduction

Thioacetamide (TAA) is a sulfur-containing compound that may be used in agriculture, as well as in rubber and paper industries and metallurgy. The hepatotoxic effects of TAA are mediated primarily by the covalent binding of TAA metabolites to macromolecules in hepatocytes (Porter et al, 1979; Dyroff and Neal, 1981). TAA was found to induce lipid peroxidation in the liver, associated with a reduction in catalase activity and reduced glutathione (GSH) level (Sanz et al, 1998). All of these mechanisms contribute to the acute bridging necrosis and apoptosis of hepatocytes after administration of 300 mg/kg TAA. Higher doses (900 mg/kg) provoke extensive inflammation with hemorrhages that lead to the development of acute liver

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