Changes in Microsomal Activity in Alcoholism and Obesity
BACKGROUND: Liver damage is more prevalent among obese alcoholics, and cytochrome P-4502E1(CYP2E1) induction is involved in its pathogenesis. OBJECTIVES: The study was undertaken to assess microsomal function, in alcoholic and nonalcoholic male subjects with different body compositions, through phar...
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2000
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| author | M. P a de la Maza Sandra Hirsch Margarita Petermann Myriam Suazo G Ugarte Daniel Bunout |
| author_browse | Daniel Bunout G Ugarte M. P a de la Maza Margarita Petermann Myriam Suazo Sandra Hirsch |
| author_facet | M. P a de la Maza Sandra Hirsch Margarita Petermann Myriam Suazo G Ugarte Daniel Bunout |
| author_sort | M. P a de la Maza |
| collection | Producción científica |
| description | BACKGROUND: Liver damage is more prevalent among obese alcoholics, and cytochrome P-4502E1(CYP2E1) induction is involved in its pathogenesis. OBJECTIVES: The study was undertaken to assess microsomal function, in alcoholic and nonalcoholic male subjects with different body compositions, through pharmacokinetics of chlorzoxazone (CLZ). We also intended to study the relationship between CLZ hydroxylation and urinary levels of 8-hydroxydiguanosine, and between CLZ levels and liver histology. METHODS: Serial measurements of CLZ serum concentration, after a 750 mg dose, were performed in 17 alcoholics (9 normal weight and 8 obese) and 21 nonalcoholic subjects (10 normal weight and 11 obese). Concentration of 6-hydroxy-chlorzoxazone (6-OH-CLZ) was determined at the second hour. Anthropometry, clinical laboratory tests, and urinary 8-hydroxydiguanosine concentrations were measured. Liver biopsies were performed in alcoholics. RESULTS: Five biopsies revealed severe lesions, one in normal-weight and four in obese patients (p = NS). Area under the curve (AUC) of CLZ was higher in normal-weight controls compared with the rest of the groups (ANOVA p = 0.001). This parameter correlated negatively with adiposity in nonalcoholic subjects and did not correlate with liver histology. 6-OH-CLZ/CLZ ratio was lower in normal-weight controls, compared with obese subjects and normal-weight alcoholics (p = 0.02). Both alcoholism and obesity were included as predictors of CLZ AUC in a multiple regression analysis. The two-factor ANOVA showed an additive effect of centripetal body fat distribution and alcoholism. Urinary 8-hydroxydiguanosine levels were extremely variable. CONCLUSIONS: Centripetal adiposity and alcoholism are associated with induction of CYP2E1. This may explain the higher prevalence of liver damage among obese alcoholics and also nonalcoholic steatohepatitis. |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/1659 |
| institution | UPeU |
| language | English |
| publishDate | 2000 |
| publishDateRange | 2000 |
| publishDateSort | 2000 |
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| spelling | oai:cris.upeu.edu.pe:20.500.15037/16592026-10-30T16:16:24ZChanges in Microsomal Activity in Alcoholism and ObesityM. P a de la MazaSandra HirschMargarita PetermannMyriam SuazoG UgarteDaniel BunoutInternal medicineMedicineEndocrinologyObesityAnalysis of varianceGastroenterologyInternal medicineMedicineEndocrinologyObesityAnalysis of varianceGastroenterologyAdultAdultAdultAlcoholism enzymologyAlcoholism enzymologyAlcoholism enzymologyAnalysis of VarianceAnalysis of VarianceAnalysis of VarianceChlorzoxazone bloodChlorzoxazone bloodChlorzoxazone bloodChlorzoxazone pharmacokineticsChlorzoxazone pharmacokineticsChlorzoxazone pharmacokineticsHumansHumansHumansLiver Cirrhosis, Alcoholic metabolismLiver Cirrhosis, Alcoholic metabolismLiver Cirrhosis, Alcoholic metabolismMaleMaleMaleMicrosomes, Liver metabolismMicrosomes, Liver metabolismMicrosomes, Liver metabolismMiddle AgedMiddle AgedMiddle AgedMuscle Relaxants, Central bloodMuscle Relaxants, Central bloodMuscle Relaxants, Central bloodMuscle Relaxants, Central pharmacokineticsMuscle Relaxants, Central pharmacokineticsMuscle Relaxants, Central pharmacokineticsObesity enzymologyObesity enzymologyObesity enzymologyCytochrome P-450 CYP2E1 metabolismCytochrome P-450 CYP2E1 metabolismCytochrome P-450 CYP2E1 metabolismHealth Sciences Medicine Pathology and Forensic Medicine Alcohol Consumption and Health EffectsLife Sciences Biochemistry, Genetics and Molecular Biology Cancer Research Carcinogens and Genotoxicity AssessmentLife Sciences Pharmacology, Toxicology and Pharmaceutics Toxicology Forensic Toxicology and Drug AnalysisBACKGROUND: Liver damage is more prevalent among obese alcoholics, and cytochrome P-4502E1(CYP2E1) induction is involved in its pathogenesis. OBJECTIVES: The study was undertaken to assess microsomal function, in alcoholic and nonalcoholic male subjects with different body compositions, through pharmacokinetics of chlorzoxazone (CLZ). We also intended to study the relationship between CLZ hydroxylation and urinary levels of 8-hydroxydiguanosine, and between CLZ levels and liver histology. METHODS: Serial measurements of CLZ serum concentration, after a 750 mg dose, were performed in 17 alcoholics (9 normal weight and 8 obese) and 21 nonalcoholic subjects (10 normal weight and 11 obese). Concentration of 6-hydroxy-chlorzoxazone (6-OH-CLZ) was determined at the second hour. Anthropometry, clinical laboratory tests, and urinary 8-hydroxydiguanosine concentrations were measured. Liver biopsies were performed in alcoholics. RESULTS: Five biopsies revealed severe lesions, one in normal-weight and four in obese patients (p = NS). Area under the curve (AUC) of CLZ was higher in normal-weight controls compared with the rest of the groups (ANOVA p = 0.001). This parameter correlated negatively with adiposity in nonalcoholic subjects and did not correlate with liver histology. 6-OH-CLZ/CLZ ratio was lower in normal-weight controls, compared with obese subjects and normal-weight alcoholics (p = 0.02). Both alcoholism and obesity were included as predictors of CLZ AUC in a multiple regression analysis. The two-factor ANOVA showed an additive effect of centripetal body fat distribution and alcoholism. Urinary 8-hydroxydiguanosine levels were extremely variable. CONCLUSIONS: Centripetal adiposity and alcoholism are associated with induction of CYP2E1. This may explain the higher prevalence of liver damage among obese alcoholics and also nonalcoholic steatohepatitis.Articlehttps://pubmed.ncbi.nlm.nih.gov/1083290110.1097/00000374-200005000-00004https://hdl.handle.net/20.500.15037/1659W2073789511enAlcoholism Clinical and Experimental Research0145-60081530-02772000-05-012026-06-13T14:18:02Z2026-06-13T14:18:02Z |
| spellingShingle | Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Adult Adult Adult Alcoholism enzymology Alcoholism enzymology Alcoholism enzymology Analysis of Variance Analysis of Variance Analysis of Variance Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Humans Humans Humans Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Male Male Male Microsomes, Liver metabolism Microsomes, Liver metabolism Microsomes, Liver metabolism Middle Aged Middle Aged Middle Aged Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Obesity enzymology Obesity enzymology Obesity enzymology Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Health Sciences Medicine Pathology and Forensic Medicine Alcohol Consumption and Health Effects Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research Carcinogens and Genotoxicity Assessment Life Sciences Pharmacology, Toxicology and Pharmaceutics Toxicology Forensic Toxicology and Drug Analysis M. P a de la Maza Sandra Hirsch Margarita Petermann Myriam Suazo G Ugarte Daniel Bunout Changes in Microsomal Activity in Alcoholism and Obesity |
| title | Changes in Microsomal Activity in Alcoholism and Obesity |
| title_full | Changes in Microsomal Activity in Alcoholism and Obesity |
| title_fullStr | Changes in Microsomal Activity in Alcoholism and Obesity |
| title_full_unstemmed | Changes in Microsomal Activity in Alcoholism and Obesity |
| title_short | Changes in Microsomal Activity in Alcoholism and Obesity |
| title_sort | changes in microsomal activity in alcoholism and obesity |
| topic | Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Adult Adult Adult Alcoholism enzymology Alcoholism enzymology Alcoholism enzymology Analysis of Variance Analysis of Variance Analysis of Variance Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Humans Humans Humans Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Male Male Male Microsomes, Liver metabolism Microsomes, Liver metabolism Microsomes, Liver metabolism Middle Aged Middle Aged Middle Aged Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Obesity enzymology Obesity enzymology Obesity enzymology Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Health Sciences Medicine Pathology and Forensic Medicine Alcohol Consumption and Health Effects Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research Carcinogens and Genotoxicity Assessment Life Sciences Pharmacology, Toxicology and Pharmaceutics Toxicology Forensic Toxicology and Drug Analysis |
| topic_facet | Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Internal medicine Medicine Endocrinology Obesity Analysis of variance Gastroenterology Adult Adult Adult Alcoholism enzymology Alcoholism enzymology Alcoholism enzymology Analysis of Variance Analysis of Variance Analysis of Variance Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone blood Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Chlorzoxazone pharmacokinetics Humans Humans Humans Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Liver Cirrhosis, Alcoholic metabolism Male Male Male Microsomes, Liver metabolism Microsomes, Liver metabolism Microsomes, Liver metabolism Middle Aged Middle Aged Middle Aged Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central blood Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Muscle Relaxants, Central pharmacokinetics Obesity enzymology Obesity enzymology Obesity enzymology Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Cytochrome P-450 CYP2E1 metabolism Health Sciences Medicine Pathology and Forensic Medicine Alcohol Consumption and Health Effects Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research Carcinogens and Genotoxicity Assessment Life Sciences Pharmacology, Toxicology and Pharmaceutics Toxicology Forensic Toxicology and Drug Analysis |
| url | https://pubmed.ncbi.nlm.nih.gov/10832901 https://hdl.handle.net/20.500.15037/1659 |
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