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首页> 外文期刊>Journal of applied toxicology >Effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity - an in vitro study.
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Effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity - an in vitro study.

机译:选定的醇脱氢酶抑制剂对人肝乳酸脱氢酶活性的影响-一项体外研究。

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Metabolic acidosis severely complicates methanol and ethylene glycol intoxications. Acidosis is caused by acid metabolites and can be intensified by lactate elevation. Lactate concentration depends on the NADH(2)/NAD ratio. Lactate dehydrogenase (LDH, E.C.1.1.1.27.) supplies more lactate when the level of NADH(2) is elevated. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH) inhibitors and substrates: cimetidine, EDTA, 4-methylpyrazole (4-MP), Ukrain and ethanol on LDH activity. The activity of LDH was determined spectrophotometrically in human liver homogenates incubated with cimetidine, EDTA, 4-MP and Ukrain at concentrations of 2 x 10(-6), 10(-5) and 5 x 10(-5) m as well as ethanol at concentrations of 12.50, 25.00, 50.00 mm. The LDH activity was significantly increased by 10(-5) and 5 x 10(-5) m concentrations of cimetidine and 4-MP, and by all concentrations of ethanol. The most effective change of LDH activity of about 26% (P<0.01) was observed at the highest concentration of ethanol. Ukrain inhibited LDH activity at both concentrations, i.e. 10(-5) and 5 x 10(-5) m (P<0.05). However, EDTA did not significantly influence LDH activity. The data showed that ethanol and 4-MP, the main antidotes in methanol or ethylene glycol poisoning, may increase liver LDH activity - an undesirable effect during the therapy of patients intoxicated with these alcohols. On the other hand, the decrease of LDH activity in the presence of Ukrain is a promising finding but definitely requires further investigation.
机译:代谢性酸中毒使甲醇和乙二醇中毒严重加重。酸中毒是由酸代谢产物引起的,并可因乳酸升高而加剧。乳酸浓度取决于NADH(2)/ NAD比率。当NADH(2)水平升高时,乳酸脱氢酶(LDH,E.1.C.1.1.27。)提供更多的乳酸。该研究的目的是评估醇脱氢酶(ADH)抑制剂和底物:西咪替丁,EDTA,4-甲基吡唑(4-MP),乌克兰和乙醇对LDH活性的影响。用分光光度法测定在2 x 10(-6),10(-5)和5 x 10(-5)m浓度的西咪替丁,EDTA,4-MP和Ukrain孵育的人肝匀浆中LDH的活性,以及浓度为12.50、25.00、50.00毫米的乙醇。 LDH活性显着增加了10(-5)和5 x 10(-5)m浓度的西咪替丁和4-MP,以及所有浓度的乙醇。在最高乙醇浓度下,LDH活性最有效的变化约为26%(P <0.01)。乌克兰在两种浓度下(10(-5)和5 x 10(-5)m)均抑制LDH活性(P <0.05)。但是,EDTA并未显着影响LDH活性。数据显示,乙醇和4-MP是甲醇或乙二醇中毒的主要解毒剂,可能会增加肝脏LDH活性-在治疗被这些醇中毒的患者期间,这是不良的作用。另一方面,存在乌克兰的情况下LDH活性降低是一个有前途的发现,但绝对需要进一步研究。

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