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排序方式: 共有423条查询结果,搜索用时 15 毫秒
1.
中国蒙,汉族酒依赖与醇脱氢酶和醛脱氢酶基因多态性的相关研究 总被引:7,自引:1,他引:6
为探讨醇脱氢酶(ADH)基因和醛脱氢酶(ALDH)基因多态性与酒依赖患病的相互关系,用耳血干血痕聚合酶链反应、等位基因特异性寡核苷酸探针方法,检测乙醇代谢酶ADH和ALDH基因型在我国蒙、汉民族酒依赖与非酒依赖者中分布频率。结果显示在酒依赖组(汉族52例,蒙族31例)与正常对照组(汉族48例,蒙族35例)之间:汉族的ALDH2基因型频率与等位基因频率的分布差异有非常显著性(P<0.01),而蒙族则表示为ADH2基因型频率与等位基因频率的分布差异有非常显著性(P<0.01)。这提示汉族酒依赖的发病与ALDH2基因有关,蒙族则与ADH2基因有关。 相似文献
2.
A hepatic soluble aldehyde dehydrogenase (ALDH), inducible by polycyclic aromatic hydrocarbons, was studied in Wistar rats in connection with substances known to affect drug metabolism or aldehyde dehydrogenase activity, such as phenobarbital (PB), disulfiram (DS), -diethylaminoethyl diphenylpropylacetate (SKF 525A) and calcium cyanamide (CC). 3-Methylcholanthrene (MC) was given as a model inducer of ALDH (100 mg/kg, i.p., as a single dose) and the animals were killed after 3 days. Pretreatment with PB (1 g/l drinking water, for 2 weeks) enhanced the inducing effect of MC. On the contrary, pretreatment with DS (100 mg/kg, i.p., daily x4) reduced by 70% the expected increase in ALDH activity. Neither SKF 525A (25 mg/kg, i.p., daily x4), nor CC (5 mg/kg, i.p., daily x4) could affect the action of the inducer. At the above doses, basal ALDH activity was inhibited by DS (30%) and CC (70%), but was not affected at all by PB or SKF 525A. The results were somewhat different when the various effectors tested were administered to animals already treated with MC (20 mg/kg, i.p., daily x6). In this case, DS did not affect the already induced ALDH activity. On the contrary, CC was still an effective inhibitor. Unexpectedly, post-treatment with SKF 525A further enhanced the initial induction brought about by MC. Our findings show that substances affecting microsomal drug metabolism can interfere with the process of ALDH induction by MC. The additive result of PB pretreatment is probably due to the enhanced accumulation of an active metabolite of MC. The opposite effect of DS on drug metabolism could explain the decreased ability of MC to induce ALDH activity. The MC-inducible ALDH isozyme can be effectively inhibited with CC, but not with DS. 相似文献
3.
应用荧光偏振技术探讨酒精及其代谢产物乙醛对与神经细胞发育分化相关的星形胶质细胞膜脂质荧光偏振度(Pr)和流动度(LFU)的影响。结果表明低剂量酒精、乙醛并不影响星形胶质细胞膜脂荧光偏振度和流动度,而在中剂量以上均可影响星形胶质细胞的Pr值,导致荧光偏振度降低,而细胞膜脂质流动度增高,均与酒精、乙醛剂量显著相关。同剂量酒精、乙醛对星形胶质细胞作用和流动度增加无显著性差异。但酒精、乙醛均可导致星形胶质细胞膜脂质流动性增加,致使细胞膜的结构改变。 相似文献
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Nádia M. Grilo Catarina Charneira Sofia A. Pereira Emília C. Monteiro M. Matilde Marques Alexandra M.M. Antunes 《Toxicology letters》2014
Aldehydes are highly reactive molecules, which can be generated during numerous physiological processes, including the biotransformation of drugs. Several non-P450 enzymes participate in their metabolism albeit alcohol dehydrogenase and aldehyde dehydrogenase are the ones most frequently involved in this process. Endogenous and exogenous aldehydes have been strongly implicated in multiple human pathologies. Their ability to react with biomacromolecules (e.g. proteins) yielding covalent adducts is suggested to be the common primary mechanism underlying the toxicity of these reactive species. 相似文献
6.
《Annals of epidemiology》2014,24(8):606-611
PurposeIn Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function.MethodsWe examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1 second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression.ResultsALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1 second −1.52%, 95% confidence interval [CI], −2.52% to −0.51% for one inactive allele and −2.05%, 95% CI, −3.85% to −0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity −1.25%, 95% CI −2.15% to −0.35% and −1.65%, 95% CI, −3.25% to −0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders.ConclusionsPrevious findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease. 相似文献
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8.
S-methyl N,N -diethylthiolcarbamate sulfoxide (DETC-MeSO) is a potent inhibitor of rat liver mitochondrial low K m aldehyde dehydrogenase (ALDH2 ) both in vivo and in vitro, and has been proposed to be the metabolite responsible for ALDH2 inhibition by disulfiram. Diethyldithiocarbamate methyl ester (DDTC-Me), a key intermediate in the metabolism of disulfiram, has been shown to be bioactivated by microsomal monooxygenases to diethyldithiocarbamate methyl ester sulfoxide (DDTC-Me sulfoxide). Studies were conducted to determine if DDTC-Me sulfoxide was also an active metabolite of disulfiram and inhibitor of ALDH2 . DDTC-Me sulfoxide inhibited ALDH2 in vitro with an IC50 of 10 μm, and in vivo with an ID50 of 31 mg/kg (170 μmol/kg). Maximal ALDH2 inhibition in vivo was observed 8 hr after the administration of 45.2 mg/kg DDTC-Me sulfoxide, with ALDH2 activity returning to control levels after 48 hr. Although DDTC-Me sulfoxide inhibited ALDH2 in vivo, DDTC-Me sulfoxide was not detected in plasma from rats treated with either disulfiram (75 mg/kg), DDTC-Me (122.25 mg/kg), or DDTC-Me sulfoxide (45.2 mg/kg). However, DDTC-Me and S -methyl N,N -diethylthiolcarbamate (DETC-Me) were detected in plasma from rats treated with DDTC-Me sulfoxide. In rats treated with DDTC-Me sulfoxide and challenged with ethanol, a small increase of ∼9 μm in blood acetaldehyde and an inconsistent drop in blood pressure was observed. In conclusion, DDTC-Me sulfoxide inhibited ALDH2 in vitro and in vivo, was less potent than DETC- MeSO, and was not detected after disulfiram administration. 相似文献
9.
Association of the ADH2 genotypes with skin responses after ethanol exposure in Japanese male university students 总被引:2,自引:0,他引:2
BACKGROUND: A contribution of the alcohol dehydrogenase-2 (ADH2) polymorphism to alcohol sensitivity and alcohol drinking behavior is still controversial. In this study, we examined the effects of the ADH2 genotypes on skin reactions to ethanol and habitual alcohol intake among Japanese male university students, controlling for the effects of the low Km aldehyde dehydrogenase (ALDH2) genotype, as an extension of our previous study. METHODS: The study subjects were 357 Japanese male students [average age (mean +/- SD) was 23.7 +/- 3.0 years] in a medical university. The subjects completed a questionnaire regarding self-reported alcohol-associated symptoms and alcohol-drinking behavior. The ADH2 and ALDH2 genotypes were determined through digestion of polymerase chain reaction products by restriction enzymes. All subjects participated in the ethanol patch test. We observed skin responses at 0, 5, 15, and 20 min after removal of the tape. RESULTS: Among the ALDH2*1/*1 genotypes, only some subjects with ADH2*1/*2 or ADH2*2/*2 exhibited a positive response, which increased with increasing time after the removal. However, none of comparisons between the different ADH2 genotypes reached statistical significance. Among the ALDH2*1/*2 genotypes, those with ADH2*1/*2 or ADH2*2/*2 showed a significant increase in response with increasing time after the removal and revealed a significantly higher positivity rate at 15 min than those with ADH2*1/*1. In those with the ALDH2*1/*2 genotype, the positive rate of facial flushing with one glass of beer was higher in those with ADH2*1/*2 and ADH2*2/*2 than those with ADH2*1/*1, although this was not significant. However, the ADH2 genotype did not seem to influence drinking frequency or amounts of alcohol intake in each ALDH2 genotype. CONCLUSIONS: This study finds further evidence for a contribution of the ADH2 polymorphism to skin reactions after either local or systemic ethanol exposure in Asian people. However, the effects of the ADH2 polymorphism may be mild because this polymorphism does not seem to influence alcohol drinking behavior in these study subjects. 相似文献
10.