乙醇对胃乙醇脱氢酶活性变化的影响

目的：探讨乙醇对胃乙醇脱氢酶（Alcohol dehydrogenase,ADH)活性变化的影响。方法：Wistar大鼠52只随机分成两组：模型组32只,对照组20只。用乙醇直接灌胃的方法建立大鼠模型;用酶组织细胞化学染色技术,观察胃ADH活性变化,并用LUZEX－F灰度图像分析仪进行半定量。结果：随着乙醇灌注量的增加和灌注时间的延长,胃ADH活性进行性下降,与对照组有显著性差异（P＜0．05）;停止灌注后1个月,胃ADH活性明显恢复,且与正常对照组无显著性差异（P＞0．05）。结论：乙醇导致胃ADH活性进行性下降,从而降低了乙醇首过代谢,增加了乙醇对肝脏等器官的毒害作用。     

肝胃乙醇脱氢酶活性变化与酒精性肝病发生的关系

目的 探讨肝、胃乙醇脱氢酶（ADH）活性的变化在酒精性肝病（ALD）不同病理阶段中的作用。方法 Wistar大鼠39只随机分成两组：模型组24只,对照组15只,用乙醇直接灌胃的方法建立大鼠ALD模型;用酶组织细胞化学染色技术,观察ALD不同病理阶段肝、胃ADH活性变化,并用LUZEX－F灰度图像分析仪进行ADH半定量。结果 ALD不同病理阶段肝ADH活性进行性增加,胃ADH活性进行性下降,两者均与对照组比较差异有显著性（P＜0．05）。结论 肝、胃ADH活性变化可能在ALD发生发展中起重要作用。     

单味鲜葛花汁对急性酒精中毒大鼠乙醇代谢的影响

目的:观察鲜葛花汁对急性酒精中毒大鼠体内乙醇代谢的影响,探讨鲜葛花汁预防醉酒作用的机制。方法:90只大鼠随机分为正常组、模型组、鲜葛花汁大、中、小剂量组和海王金樽组,除正常组外,其余各组大鼠均用白酒灌胃法造模。采用乙醇干片试剂法分别测定末次灌胃后1、2、3、5小时大鼠血中乙醇浓度;用比色法测定大鼠肝、胃组织乙醇脱氢酶(ADH)活性的变化;分别用黄嘌呤氧化酶法、TBA法、比色法检测大鼠肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的含量。结果:鲜葛花汁各组大鼠血中乙醇浓度低于模型组,差异有显著性意义(P<0.01);鲜葛花汁各组大鼠肝、胃组织ADH活性高于模型组(P<0.05),鲜葛花汁可显著提高大鼠肝组织SOD、GSH-Px水平,降低MDA水平,与模型组相比差异有显著性意义(P<0.01)。结论:鲜葛花汁通过提高ADH活性,加强乙醇在胃肠道的首过效应,降低血中的乙醇浓度,激活微粒体乙醇氧化系统(MEOS),加速乙醇及其代谢产物的消除速率,达到解酒的目的。     

人胃细胞的酒精代谢:与首过代谢的关系

用等量的酒精静脉注射和口服,前者血液酒精浓度更高,说明口服酒精生物利用度不完全,提示存在首过代谢。酒精的首过代谢十分重要,当它受损时,有更多的酒精进入血液循环,可能会造成酒精中毒。本研究用人胃上皮细胞的原代培养测试酒精至乙酸盐的代谢,并将之与体内首过代谢量比较,以证实胃的乙醇脱氢酶(ADH)在酒精首过代谢中的作用。     

乳酸菌对酒精引起的胃粘膜和肝脏损伤的保护作用

探讨乳酸菌混合液对酒精引起的胃粘膜及肝脏的损伤保护作用。 2 5只Wistar大鼠 ,分为乳酸菌保护组、酒精攻击组和对照组 ,共服用 5天。生化检测指标为乳酸菌乙醇脱氢酶 (ADH)、血中乙醇含量 (30分钟和 3小时 )、内毒素水平 ,并行胃、肝脏病理检查。结果显示每毫克乳酸菌蛋白质中ADH活性单位为 3 85U。服用酒精后30分钟及 3小时乳酸菌保护组动物血中乙醇浓度低于酒精攻击组 (P <0 0 0 5 ) ;乳酸菌保护组血清内毒素水平明显低于酒精攻击组 (P <0 0 1)。病理检查结果 :酒精攻击组大多数显示胃粘膜糜烂 ,上皮细胞脱落 ,肝脏严重大泡性脂变 ,而乳酸菌保护组胃和肝脏组织学基本正常。乳酸菌液通过保护胃粘膜减少酒精从胃内的吸收 ,减少细菌 /内毒素移位 ,起到预防酒精性肝损伤的作用。     

枳黄方对酒精性肝损伤大鼠肝胃ADH1 mRNA的影响

目的:探讨枳黄方对大鼠酒精性肝损伤的防护作用及其机理。方法:将30只SD大鼠随机分为3组:空白对照组、酒精攻击组、枳黄方防护组,每组10只。10天后,处死大鼠,取大鼠肝脏进行HE染色观察肝病理变化,RT-PCR法测定肝、胃组织ADH1mRNA的变化。结果:枳黄方能缩短大鼠醉酒时间(P<0.05),枳黄方防护组肝、胃病理表现较模型组明显改善,其肝、胃ADH1mRNA表达量高于模型组(P<0.01)。结论:枳黄方对大鼠酒精性肝损伤有较明显的防护作用,这可能与其能提高肝、胃ADH1mRNA的表达有关。     

黄瓜香提取物对大鼠酒精性肝损伤氧化应激的实验研究

[目的]研究黄瓜香提取物对大鼠酒精性肝损伤的改善作用,探讨其可能的作用机制。[方法]健康雄性大鼠45只,随机分为3组:对照组、模型组和黄瓜香提取物组,模型组和黄瓜香提取物组灌以酒精8周,建立大鼠酒精性肝损伤模型,黄瓜香提取物组同时给予黄瓜香提取物7.5 g/(kg.d)进行预防治疗,测定血清丙氨酸氨基转移酶(ALT),门冬氨酸氨基转移酶(AST),血清和肝脏三酰甘油(TG)水平、苯胺羟化酶(ANH)、乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)活性等生化指标,并进行病理组织学观察。[结果]黄瓜香提取物能够降低血清ALT、AST、TG水平,降低肝脏TG水平,此外,黄瓜香提取物还可使微粒体ANH活性降低,使细胞质中ADH和ALDH活性升高,同时,降低肝组织丙二醛含量,升高肝组织超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。[结论]黄瓜香提取物对酒精性肝损伤具有保护作用,其机制与加速乙醇和乙醛的清除,调控酒精代谢过程,提高机体抗氧化能力有关。     

血清乙醇脱氢醇在肝病时的意义

乙醇脱氢酶(ADH)主要存在于肝细胞浆中、在胃、肠、肾、网膜及脑组织则仅有少量。该酶与乙醇代谢有关,当肝实质损害时,ADH逸入血中,血清ADH(S-ADH)即见升高。作者对108例各种肝脏病患者和17例嗜酒者用Mezey法测定S-ADH活性,并与41例非肝病患者作比较,其结果和临床意义如下:     

枳葛口服液防治大鼠酒精性肝病的相关机制

目的探讨枳葛口服液对酒精性肝病模型大鼠的防治作用及分子机制.方法以酒精灌胃加普通饲料造模酒精性肝损伤大鼠,干预组酒精灌胃同时给予不同剂量(高、中、低剂量)枳葛口服液,对照组酒精灌胃同时给予解酒灵口服液.12 wk后处死动物检测各组大鼠肝功、肝脏指数、脂质代谢、氧化应激及乙醇代谢酶活性等相关指标,同时观察各组肝组织病理学变化.结果相比正常组,除高剂量组外,各组大鼠肝脏指数、谷丙转氨酶、谷草转氨酶、总胆固醇、三酰甘油、乙醇脱氢酶(alcohol dehydrogenase,ADH)、乙醛脱氢酶(aldehyde dehydrogenase,ALDH)及CYP450 2E1含量均有明显变化(P0.01或0.05),且各组肝组织HE染色可见不同程度大面积的泡性脂肪空泡,其中模型组和枳葛口服液低剂量组差异最大(P0.01).相比模型组,各治疗组以上指标均呈现不同程度地逆转(P0.01或0.05),其中高剂量组逆转最显著(P0.01).枳葛口服液中剂量组疗效与解酒灵口服液对照组疗效近似(P0.05).结论枳葛口服液解酒护肝之功效可能与逆转ADH、ALDH等乙醇代谢酶活性进而抑制自由基、乙醛生成,抑制机体氧化应激,改善大鼠脂质代谢紊乱等密切相关.     

清肝活血方对酒精性肝病大鼠ADH及CYPⅡE1的影响

目的：观察清肝活血方对酒精性肝病大鼠乙醇代谢关键酶基因表达的影响。方法：用乙醇、玉米油、吡唑等制备酒精性肝病大鼠模型。RR－PCR法检测大鼠肝组织ADH及P450ⅡE1mRNA表达。结果：酒精性肝病大鼠模型表现为肝功能异常，以AST变化为显著；模型组AH活性及其mRNA与P450ⅡE1mRNA表达下降；高剂量清肝活血方组大鼠ADH活性及ADH与P450ⅡE1mRNA的表达显著提高。结论：清肝活血方能显著提高模型组大鼠ADH活性及ADH与YPⅡE1mRNA的表达，促进肝脏的解毒功能。     

Zinc Administration Improves Gastric Alcohol Dehydrogenase Activity and First-Pass Metabolism of Ethanol in Alcohol-Fed Rats

The effects of zinc on first-pass metabolism (FPM) of ethanol and gastric and hepatic alcohol dehydrogenase (ADH) activities have been investigated in two groups of male Wistar rats fed a liquid ethanol diet with normal zinc content (7.6 mg/liter), or zinc supplemented (76 mg/liter), for 21 days, and in two pair-fed groups receiving the same diets without ethanol. Alcoholic rats with normal dietary zinc had lower FPM (1.64 ± 0.25 vs. 2.43 ± 0.20 mM ± hr, p < 0.05) and gastric ADH activity (184 ± 7 vs. 335 ± 41 μmol/min/mg protein, p < 0.01) than control rats. Zinc supplementation did not produce any change in FPM or in gastric ADH activity in control rats. By contrast, in alcoholic rats, the zinc supplement increased gastric ADH activity (247 ± 31 vs. 184 ± 7 μmol/min/mg protein, p < 0.05) and decreased the areas under the curve of blood ethanol concentrations after the intragastric administration of 0.25 g/kg of body weight of ethanol (0.78 ± 0.07 vs. 1.71 ± 0.24 mM ± hr, p < 0.05), thereby increasing the FPM. In conclusion, in alcohol-fed rats, the administration of zinc supplements restores gastric ADH activity and improves the FPM of ethanol. These effects may be one of the mechanisms in which zinc has a beneficial role in preventing the development of alcoholic hepatic lesions.     

Role of Catalase in Rat Gastric Mucosal Ethanol Metabolism In Vitro

To evaluate the possible role of catalase in gastric ethanol metabolism in rats, we studied acetaldehyde formation from ethanol by gastric mucosal homogenate under various in vitro conditions. Homogenized rat gastric mucosa produced significant amounts of acetaldehyde in a time and ethanol concentration-dependent manner, even in the absence of added NAD. Both acetaldehyde formation and catalase activity peaked around the physiological pH, whereas alcohol dehydrogenase (ADH) activity was in that pH range low and reached peak values only at a higher pH of 9 to 10. Catalase inhibitors sodium azide (SA) and 3-amino-1,2,4-triazole (3-AT) had little effect on ADH activity but markedly decreased catalase activity and acetaldehyde formation (1 mM of SA to 56 ± 13% of control, 5 mM of 3-AT to 67 ± 3% of control; mean ± SE). 4-Methylpyrazole decreased ADH activity significantly, but did not affect acetaldehyde formation. Heating of the homogenate at 60°C for 5 min decreased ADH activity only slightly, but totally abolished catalase activity and reduced acetaldehyde formation to 39 ± 3% of control. Addition of a H₂O₂ generating system [β- d (+)-glucose + glucose oxidase] increased acetaldehyde formation in a concentration-dependent manner up to 8-fold of the control value. Our results strongly suggest that, in addition to ADH, catalase may play a significant role in gastric ethanol metabolism in rats.     

Contribution of gastric oxidation to ethanol first-pass metabolism in baboons

BACKGROUND: A portion of ingested alcohol does not reach the systemic blood, undergoing a first-pass metabolism (FPM) during gastric and hepatic circulation. METHODS: To determine whether the stomach can metabolize sufficient ethanol to account for the FPM, and to what extent gastric alcohol dehydrogenase (ADH) activity is responsible, the hepatic vein, the portal vein, and the aorta were cannulated nonocclusively in baboons to measure the conversion of ethanol to acetate in vivo. 14C-ethanol (300 mg/kg as a 15% solution) was given intragastrically (IG) whereas 3H-acetate was continuously infused intravenously (IV). 14C-acetate was measured after exhaustive evaporation of ethanol. Simultaneous sampling of hepatic venous, portal and arterial blood was carried out for 3 hr, at the end of which the same alcohol dose was given IV to calculate the Michaelis-Menten parameters of elimination. RESULTS: Analysis of the IV and IG ethanol curves revealed a FPM of 94+/-11 mg/kg (31% of dose). The portal-arterial differences were negative for 3H-acetate (indicating net extraction) and positive for 14C-ethanol and 14C-acetate (indicating net output). Portal acetate production (extraction plus net output multiplied by the portal plasma flow) increased with time and accounted, over the first 3 hr (82+/-13 mg/kg), for 87% of the FPM. Alcohol oxidation by gastric ADH activity (28.7+/-7.2 mg/kg) accounted for only 31% of the FPM. CONCLUSIONS: The in vivo oxidation of ethanol to acetate in the upper digestive tract accounts for the FPM of ethanol and is mediated, at least in part, by ADH activity.     

Alcohol Dehydrogenase (ADH) Isoenzymes and Aldehyde Dehydrogenase (ALDH) Activity in the Sera of Patients with Gastric Cancer

BACKGROUND: Investigations have shown that alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in some cancer cells and can play role in carcinogenesis. In recent experiments we found elevated alcohol dehydrogenase class IV activity in gastric cancer cells. This suggests these changes may be reflected by enzyme activity in the serum. AIM: In this work we measured the activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in the sera of patients with gastric cancer matched on gender. METHODS: Serum samples were taken for routine biochemical investigation from 55 patients with gastric cancer, before treatment, and from 55 control subjects. Total ADH activity was measured photometrically and ALDH activity by a fluorimetric method. For measurement of the activity of class I isoenzymes we used a fluorimetric method, with class-specific fluorogenic substrates. The activity of class III and IV alcohol dehydrogenase was measured photometrically. RESULTS: The activity of the class IV ADH isoenzyme was significantly higher in the sera of patients with gastric cancer. The median activity of this isoenzyme in the total cancer group was approximately 47% higher (7.45 mU/l) than the control level (5.08 mU/l). For this reason total ADH activity was also significantly increased. The activities of other tested ADH isoenzymes and ALDH were unchanged. CONCLUSION: Changes in the activity of, especially, class IV ADH in the sera of patients with gastric cancer seems to be caused by release of the isoenzyme from cancer cells.     

Helicobacter Infection and Gastric Ethanol Metabolism

The organism frequently colonizing the stomach of patients suffering from chronic active gastritis and peptic ulcer disease– Helicobacter pylori –possesses marked alcohol dehydrogenase (ADH) activity. Consequently, Helicobacter infection may contribute to the capacity of the stomach to metabolize ethanol and lead to increased acetaldehyde production. To study this hypothesis, we first determined ADH activity in a variety of H. pylori strains originally isolated from human gastric mucosal biopsies. ADH activity was also measured in endoscopic gastric mucosal specimens obtained from H. pylori -positive and -negative patients. Furthermore, we used a mouse model of Helicobacter infection to determine whether infected animals exhibit more gastric ethanol metabolism than noninfected controls.
Most of the 32 H. pylori strains studied possessed clear ADH activity and produced acetaldehyde. In humans, gastric ADH activity of corpus mucosa did not differ between H. pylori -positive and -negative subjects, whereas in antral biopsies ADH activity was significantly lower in infected patients. In mice, gastric ADH activity was similar or even lower in infected animals than in controls, depending on the duration of infection, despite the fact that the infectious agent used– Helicobacter felis –showed ADH activity in vitro. In accordance with this, Helicobacter infection tended to decrease rather than increase gastric ethanol metabolism in mice. In humans, it remains to be established whether the observed decrease in antral ADH activity associated with H. pylori infection can lead to reduced gastric first-pass metabolism of ethanol.     

Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism

BACKGROUND: Alcohol dehydrogenase (ADH) is the principal enzyme responsible for ethanol metabolism in mammals. Human ADH constitutes a unique complex enzyme family with no equivalent counterpart in experimental rodents. This study was undertaken to quantitatively assess relative contributions of human ADH isozymes and allozymes to hepatic versus gastric metabolism of ethanol in the context of the entire family. METHODS: Kinetic parameters for ethanol oxidation for recombinant human class I ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, and ADH1C2; class II ADH2; class III ADH3; and class IV ADH4 were determined in 0.1 M sodium phosphate at pH 7.5 over a wide range of substrate concentrations in the presence of 0.5 mM NAD+. The composite numerical formulations for organ steady-state ethanol clearance were established by summing up the kinetic equations of constituent isozymes/allozymes with the assessed contents in livers and gastric mucosae with different genotypes. RESULTS: In ADH1B*1 individuals, ADH1B1 and ADH1C allozymes were found to be the major contributors to hepatic-alcohol clearance; ADH2 made a significant contribution only at high ethanol levels (> 20 mM). ADH1B2 was the major hepatic contributor in ADH1B*2 individuals. ADH1C allozymes were the major contributor at low ethanol (< 2 mM), whereas ADH1B3 the major form at higher levels (> 10 mM) in ADH1B*3 individuals. For gastric mucosal-alcohol clearance, the relative contributions of ADH1C allozymes and ADH4 were converse as ethanol concentration increased. It was assessed that livers with ADH1B*1 may eliminate approximately 95% or more of single-passed ethanol as inflow sinusoidal alcohol reaches approximately 1 mM and that stomachs with different ADH1C genotypes may remove 20% to 30% of single-passed alcohol at the similar level in mucosal cells. CONCLUSIONS: This work provides just a model, but a strong one, for quantitative assessments of ethanol metabolism in the human liver and stomach. The results indicate that the hepatic-alcohol clearance of ADH1B*2 individuals is higher than that of the ADH1B*1 and those of the ADH1B*3 versus the ADH1B*1 vary depending on sinusoidal ethanol levels. The maximal capacity for potential alcohol first-pass metabolism in the liver is greater than in the stomach.