RESUMO
1. Caffeine has been used to determine acetylator phenotype for some 15 years but the interpretation of metabolic ratios with this substance raises theoretical and methodological issues. 2. N-acetyltransferase type 2 (NAT2) status was assessed in 23 young healthy subjects using both caffeine overnight and spot urine samples, and sulphadimidine. 3. Frequency distribution analysis of the metabolic ratios of NAT2, indicated two distinct groups for sulphadimidine, and for caffeine spot but not overnight samples. Spearman's rank correlation values were low indicating differences between the data sets for sulphadimidine and spot caffeine samples. Correlation between the two urine collection periods for caffeine was poor. 4. The complex metabolism of caffeine may compromise its value as a probe for determining acetylator phenotype until the effects of important variables are better understood.
Assuntos
Arilamina N-Acetiltransferase/metabolismo , Cafeína/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , FenótipoAssuntos
Bloqueadores dos Canais de Cálcio/síntese química , Músculo Liso/efeitos dos fármacos , Piperazinas/síntese química , Animais , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Ceco/efeitos dos fármacos , Colo/efeitos dos fármacos , Cobaias , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Piperazinas/farmacologiaRESUMO
Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N-acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP.
Assuntos
Acetiltransferases/análise , Polipose Adenomatosa do Colo/enzimologia , Sistema Enzimático do Citocromo P-450/análise , Oxirredutases/análise , Xantina Oxidase/análise , Polipose Adenomatosa do Colo/cirurgia , Polipose Adenomatosa do Colo/urina , Adolescente , Adulto , Idoso , Cafeína/urina , Colectomia , Citocromo P-450 CYP1A2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de TempoRESUMO
1. Caffeine is widely used as an in vivo probe for CYP1A2; the distribution/activity of this enzyme is reported to be reflected by metabolic ratios. 2. Several metabolic ratios using different combinations of urinary metabolites have been used to measure CYP1A2, with varying conclusions on its distribution. 3. A mathematical comparison of five metabolic ratios claiming to reflect CYP1A2 activity was made using data from 237 healthy volunteers. 4. All five metabolic ratios were symmetrically distributed. The five ratios however, measured at least three different parameters, with no one ratio correlating exactly with any other. 5. Data in the literature claiming to measure CYP1A2 using caffeine may reflect other parameters. 6. The complex metabolism of caffeine together with different parameters controlling the renal clearance of each metabolite, makes the use of urinary metabolic ratios an inaccurate probe for assessing the distribution of CYP1A2 activity in populations.
Assuntos
Cafeína/urina , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredutases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cafeína/administração & dosagem , Cafeína/farmacocinética , Café , Citocromo P-450 CYP1A2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valores de Referência , CháRESUMO
Caffeine is a popular compound for phenotyping individuals for CYP4501A2, xanthine oxidase (XO) and N-acetyltransferase (NAT) utilising urinary metabolites. The analysis is complex since at least thirteen metabolites are excreted by man. Past methods have been less than satisfactory in that either not all the metabolites have been resolved and/or extractions selective for particular groups of metabolites are required prior to chromatography. We report a method for the rapid analysis of caffeine and metabolites in urine that negates the requirement for an extraction step, and also a method for plasma analysis.
Assuntos
Cafeína/análise , Biotransformação , Cafeína/sangue , Cafeína/urina , Cromatografia Líquida de Alta Pressão , Humanos , Indicadores e ReagentesRESUMO
Using perfusion method the reactivity of rabbit femoral and ear arteries was investigated following the administration of rising noradrenaline doses in four consecutive intervals. Progressive increase of vasoconstrictive activity of vessel segments was found. Results of histological examination showed a progressive de-endothelialization of perfused vessels. The loss of endothelium increased depending on time of action and on intensity of vasoconstrictive stimuli.
