RESUMO
BACKGROUND/AIMS: Oxidative stress via generation of reactive oxygen species is suggested to be the major mechanism of alcohol-induced liver injury. We investigated the effects of glutathione peroxidase-1 and catalase double deficiency (Gpx-1(-/-)/Cat(-/-)) on liver injury and changes in the sulfur amino acid metabolism induced by binge ethanol administration. METHODS: Ethanol (5 g/kg) was administered orally to the wild-type and the Gpx-1(-/-)/Cat(-/-) mice every 12 h for a total of three doses. Mice were sacrificed 6 h after the final dose. RESULTS: The Gpx-1/Cat deficiency alone increased malondialdehyde levels in liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S-adenosylmethionine levels were decreased, however, glutathione contents were not changed. Ethanol administration to the Gpx-1(-/-)/Cat(-/-) mice increased the elevation of serum alanine aminotransferase activity, plasma homocysteine levels, hepatic fat accumulation and lipid peroxidation compared with the wild-type animals challenged with ethanol. Also the reduction of MAT activity and S-adenosylmethionine levels was enhanced, but MATI/III expression was increased significantly. CONCLUSIONS: The results indicate that Gpx-1 and Cat have critical roles in the protection of liver against binge ethanol exposure. Augmentation of ethanol-induced oxidative stress may be responsible for the impairment of the transsulfuration reactions and the aggravation of acute liver injury in the Gpx-1(-/-)/Cat(-/-) mice.
Assuntos
Acatalasia/metabolismo , Aminoácidos Sulfúricos/metabolismo , Etanol/toxicidade , Glutationa Peroxidase/deficiência , Fígado/efeitos dos fármacos , Fígado/metabolismo , Acatalasia/genética , Animais , Catalase/genética , Catalase/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Glutationa Peroxidase/genética , Fígado/lesões , Fígado/patologia , Masculino , Metabolômica , Metionina Adenosiltransferase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Glutationa Peroxidase GPX1RESUMO
Our objective was to describe respiratory disease hospitalizations among children in a community of Seoul, Republic of Korea. Discharge data (January 1995-December 2005) from Guro Hospital (Seoul, Republic of Korea) were collected from the hospital medical records office. Respiratory virus test results (March 2004-December 2005) and hospitalization charges to the National Health Insurance Corporation (January 2002-December 2005) were provided by hospital laboratory and administrative departments. Variations in hospitalizations, test results and total hospitalization-associated medical charges were described by age, clinical complaint, discharge month and length of stay. Over the 11-y period, 4247 paediatric hospitalizations for lower respiratory disease occurred. Semi-annual epidemics were identified in October-December and April-May. Among a subset (n=400) of patients, 48% had respiratory syncytial virus, 16% parainfluenza virus, 19% influenza viruses and 17% adenovirus infection. On admission, children had respiratory problems (53%), fever (39%), or other systemic problems (8%). The median charge of a lower respiratory disease hospitalization was highest in January ($1334) and lowest in October ($1076). Median hospitalization charges were highest among children 8-15 years of age compared with younger children