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Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women
Varela, Nelson M; Quiñones, Luis A; Orellana, Myriam; Poniachik, Jaime; Csendes, Attila; Smok, Gladys; Rodrigo, Ramón; Cáceres, Dante D; Videla, Luis A.
  • Varela, Nelson M; University of Chile. Faculty of Medicine. Institute of Biomedical Sciences. Molecular and Clinical Pharmacology Program. CL
  • Quiñones, Luis A; University of Chile. Faculty of Medicine. Institute of Biomedical Sciences. Molecular and Clinical Pharmacology Program. CL
  • Orellana, Myriam; University of Chile. Faculty of Medicine. Institute of Biomedical Sciences. Molecular and Clinical Pharmacology Program. CL
  • Poniachik, Jaime; University of Chile Clinical Hospital. Department of Medicine. CL
  • Csendes, Attila; University of Chile Clinical Hospital. Department of Surgery. CL
  • Smok, Gladys; University of Chile Clinical Hospital. Department of Pathological Anatomy. CL
  • Rodrigo, Ramón; University of Chile. Faculty of Medicine. Institute of Biomedical Sciences. Molecular and Clinical Pharmacology Program. CL
  • Cáceres, Dante D; University of Chile. School of Public Health. Epidemiology Division. Santiago. CL
  • Videla, Luis A; University of Chile. Faculty of Medicine. Institute of Biomedical Sciences. Molecular and Clinical Pharmacology Program. CL
Biol. Res ; 41(1): 81-92, 2008. ilus, tab, graf
Artículo en Inglés | LILACS | ID: lil-490635
ABSTRACT
CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45 percent; p=0.024) and steatosis (22 percent; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15 percent, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity.
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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Hígado Graso / Hepatitis / Hígado / Obesidad Tipo de estudio: Estudio observacional / Factores de riesgo Límite: Adulto / Femenino / Humanos Idioma: Inglés Revista: Biol. Res Asunto de la revista: Biologia Año: 2008 Tipo del documento: Artículo / Documento de proyecto País de afiliación: Chile Institución/País de afiliación: University of Chile Clinical Hospital/CL / University of Chile/CL

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Texto completo: Disponible Índice: LILACS (Américas) Asunto principal: Hígado Graso / Hepatitis / Hígado / Obesidad Tipo de estudio: Estudio observacional / Factores de riesgo Límite: Adulto / Femenino / Humanos Idioma: Inglés Revista: Biol. Res Asunto de la revista: Biologia Año: 2008 Tipo del documento: Artículo / Documento de proyecto País de afiliación: Chile Institución/País de afiliación: University of Chile Clinical Hospital/CL / University of Chile/CL