RESUMEN
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.
Asunto(s)
Acatalasia/metabolismo , Aminoácidos Sulfúricos/metabolismo , Etanol/toxicidad , Glutatión Peroxidasa/deficiencia , Hígado/efectos de los fármacos , Hígado/metabolismo , Acatalasia/genética , Animales , Catalasa/genética , Catalasa/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Glutatión Peroxidasa/genética , Hígado/lesiones , Hígado/patología , Masculino , Metabolómica , Metionina Adenosiltransferasa/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , S-Adenosilhomocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Glutatión Peroxidasa GPX1RESUMEN
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 =2 years and those 3-7 years of age. Respiratory disease hospitalizations among children demonstrated annual variations reflecting patterns of children with laboratory-confirmed respiratory viral infections. In the Republic of Korea, prospective studies that use standardized laboratory testing for respiratory pathogens in children will help to estimate the total burden of viral lower respiratory tract disease.