title: Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic failure induced by carbon tetrachloride is reversed by antioxidants.
abstract: Hepatic encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure. This disease is clinically characterized by a large variety of symptoms including motor symptoms, cognitive deficits, as well as changes in the level of alertness up to hepatic coma. Carbon tetrachloride is frequently used in animals to produce an experimental model to study the mechanisms involved in the progression of hepatic disease and the impact of various drugs on this progression. The brain is highly dependent on ATP and most cell energy is obtained through oxidative phosphorylation, a process requiring the action of various respiratory enzyme complexes located in a special structure of the inner mitochondrial membrane. In this context, we evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats submitted to acute administration of carbon tetrachloride and treated with NAC and DFX alone or in combination. Our results showed that complexes I, II and IV were inhibited after carbon tetrachloride administration and that NAC and DFX alone or in combination were able to prevent the inhibition of these enzymes. On the other hand, complex III was not affected. The participation of oxidative stress has been postulated in the hepatic encephalopathy and it is well known that the electron transport chain itself is vulnerable to damage by this species. Based on our findings, we suggest that oxidative stress may be involved in the inhibition of complexes from mitochondrial respiratory chain.
authors.affiliation: Laboratório de Fisiopatologia Experimental and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Lyziane A
authors.initials: LA
authors.lastname: Boer
authors.forename: Jordana P
authors.initials: JP
authors.lastname: Panatto
authors.forename: Diego A
authors.initials: DA
authors.lastname: Fagundes
authors.forename: Cintia
authors.initials: C
authors.lastname: Bassani
authors.forename: Isabela C
authors.initials: IC
authors.lastname: Jeremias
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Daufenbach
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Larissa
authors.initials: L
authors.lastname: Constantino
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004579:Electron Transport / Q000502:physiology*; D045222:Electron Transport Chain Complex Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D017093:Liver Failure / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D045222:Electron Transport Chain Complex Proteins; D004791:Enzyme Inhibitors; D002251:Carbon Tetrachloride