Журнал биомолекулярных исследований и терапии

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Thioacetamide-Induced Liver Cirrhosis Alters Oxidative Stress Balance and Induces Mitochondrial Respiratory Chain Inhibition in the Brain of Cirrhotic Rats

Zaky A and Bassiouny AR

Hepatic encephalopathy (HE) constitutes an intriguing complication characterized with neuropsychiatric symptoms that occurs as a consequence of acute or chronic liver disease. Subjects with hepatic encephalopathy are associated with elevated blood ammonia and other metabolites which are neurotoxic, ultimately leading to neuronal death due to oxidative stress. Evidences from previous studies suggest the implication of mitochondrial dysfunctions in oxidative stress conditions. In the current study we investigated brain oxidative metabolism and activities of mitochondrial respiratory chain complexes in rat model of Thioacetamide (TAA) –induced chronic cirrhosis. The activities of critical enzymes for mitochondrial function, Mn-superoxide dismutase, complex I and complex III were decreased progressively in the mid-brain cortex. We also evaluated creatine kinase (CK) activity as a marker of energy homeostasis that is shown to be inhibited by free radicals, and probably involved in the pathogenesis of hepatic encephalopathy, as well as glutathione peroxidase (GSH-PX), catalase and superoxide dismutase activities. SOD and catalase activities were decreased significantly but on the contrary GSH-PX activity is significantly increased at all studied time points. These results suggest that oxidative stress-associated inhibition of mitochondrial respiratory chain complexes and brain CK activities following hepatic failure may contribute, in part, to the early-stage pathogenesis of hepatic encephalopathy.