解酒保肝口服液对小鼠酒精中毒的影响

目的：观察解酒保肝口服液对小鼠醉酒实验,血清乙醇浓度和肝、胃组织乙醇脱氢酶活性的影响。方法：将生理盐水和将葛根,甘草等中药用水煎煮制成解酒保肝口服液灌服于小鼠后30min,灌服白酒,记录小鼠翻正反射消失（醉酒）至恢复（醒酒）所需时间（min),及24h内小鼠的死亡只数,另以相同操作连续6d后眼眶取血并处死动物,立即取出肝脏和胃,分别用生化比色法测定血肖乙醇浓度和肝、胃组织乙醇脱氢酶活性。结果：在醉酒实验中,。与对照组相比服用解酒保肝口服液组小鼠从饮酒到翻正反射消失（醉酒）的时间明显延长（P＜0．01）,醒酒时间明显缩短,且小鼠的死亡率明显降低（P＜0．05）,血清乙醇含量明显降低,肝脏ADH高于对照组, 结论：解酒保肝口服液具有解酒作用。     

酸奶番茄汁对急性酒精中毒小鼠解酒作用的实验研究

目的：研究酸奶番茄汁的解酒毒作用及其机制。方法：测定服用酸奶番茄汁前后小鼠翻正反射消失和恢复时间、血清乙醇浓度及小鼠肝、胃细胞匀浆中乙醇脱氢酶的活力变化。结果：酸奶番茄汁可缩短翻正反射恢复时间．降低醉酒小鼠血清乙醇含量,提高肝、胃组织乙醇脱氢酶的活性,且比单用酸奶和番茄汁效果更好。结论：酸奶番茄汁对预防和治疗醉酒有较好的作用,其饥制与增强肝脏对乙醇的生物转化功能及降解乙醇有关。     

葛根、葛花、枳椇子混合物对小鼠急性酒精中毒醒酒作用的研究

目的 探讨中药葛根、葛花、枳椇子混合物对小鼠急性酒精中毒的醒酒效果。方法 采用酒精灌胃法建立小鼠急性酒精中毒模型,观察混合物不同配比对小鼠的醒酒效果,选择最佳配比;按最佳配比将小鼠分为低剂量组和高剂量组,通过测定小鼠的耐受时间、醉酒时间、血液中的乙醇浓度和肝中乙醇脱氢酶的活性观察葛根、葛花、枳椇子混合物的醒酒效果。结果 葛根、葛花、枳椇子混合物能够增加小鼠对酒精的耐受时间,同时缩短小鼠的醉酒时间,降低血液中的乙醇浓度,提高肝中乙醇脱氢酶的活性。结论 葛根、葛花、枳椇子混合物对小鼠急性酒精中毒具有醒酒作用。     

海参岩藻聚糖硫酸酯对小鼠急性酒精中毒防治作用的研究

目的研究海参岩藻聚糖硫酸酯(fucoidan isolatedfrom sea cucumber,SC-FUC)对小鼠急性酒精中毒的防治作用。方法将♂ICR小鼠随机分为5组:正常对照组、模型对照组、益肝灵阳性对照组、SC-FUC低、高剂量组(50和100mg.kg-1.d-1),连续灌胃SC-FUC 4 d,于末次给药后1 h按体重灌胃乙醇体积分数为56%的白酒(15 ml.kg-1),分别记录醉酒和醒酒时间,检测血清丙氨酸氨基转移酶(ala-nine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspar-tate aminotransferase,AST)活性,肝脏中乙醇脱氢酶(alcoholdehydrogenase,ADH)、乙醛脱氢酶(acetaldehyde dehydrogen-ase,ALD)、谷胱甘肽过氧化酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase,CAT)活性,以及丙二醛(malondialdehyde,MDA)含量。结果 SC-FUC能有效推迟小鼠的醉酒时间,缩短醒酒时间,明显降低小鼠血清ALT和AST活力(P<0.01),提高肝脏ADH、ALD和抗氧化酶GSH-Px和CAT活力,降低MDA含量,对SOD活力无明显影响。结论 SC-FUC能明显促进乙醇在小鼠肝脏中的代谢速度,提高肝脏的抗氧化能力,具有较好的防治醉酒和保护肝脏作用。     

加味醒酒汤解酒作用的研究

目的 研究加味醒酒汤对醉酒小鼠的解酒作用。方法 根据建立的小鼠醉酒模型,通过测定小鼠醉酒潜伏期与醒酒时间,确定加味醒酒汤的最佳工艺;通过测定小鼠血液乙醇浓度的含量及肝脏乙醇代谢酶的活性来观察加味醒酒汤的解酒效果。结果 加味醒酒汤能够增加小鼠对酒精的耐受时间,同时缩短小鼠的醒酒时间,降低血液中的乙醇浓度,提高肝脏中ADH、ALDH与GSH-Px的活性。结论 加味醒酒汤对醉酒小鼠具有解酒作用,其机制可能与提高乙醇代谢酶的活性有关。     

醒酒护肝口服液的安全性评价及抗醉、解酒作用的研究

目的考察醒酒护肝VI服液的安全性并评价其抗醉、解酒作用。方法醒酒护肝口服液以最大浓度、最大给药剂量灌胃小鼠,观察24h内动物急性毒性反应及死亡情况,并继续观察14d以评价其安全性,同时计算小鼠最大耐受剂量;建立小鼠酒精致醉模型,以自主活动数、翻正反应消失时间及恢复时间评价醒酒护肝口服液抗醉、解酒作用。结果醒酒护肝口服液小鼠最大给药剂量为350．0g/kg,在24h内未见实验动物急性毒性反应和死亡,14d实验周期内,小鼠体质量呈进行性增长,肝功能指标未见异常;抗醉实验中,醒酒护肝口服液能显著降低致醉小鼠自主活动次数、延长醉酒时间并缩短醉睡时间：解酒实验中．醒酒护肝口服液提高醉酒时间、醉睡时间。结论醒酒护肝口服液临床剂量是合理安全的,对酒精致醉模型小鼠有抗醉作用。     

醒酒浓缩液的药效学研究

目的观测醒酒浓缩液对醉酒小鼠防醉和解酒作用。方法采用醉酒模型并测试小鼠翻正反射消失时间及恢复时间（min），气相色谱检测血中乙醇含量。结果(1)30mL/kg、40mL/kg醒酒浓缩液对醉酒小鼠具有明显防醉和解酒作用（P<0.05～0.01）；（2）醉酒前给小鼠ig醒酒浓缩液，中、高剂量组能明显降低酒后40～120min内血液中乙醇含量（P<0.05～0.01）。结论本品具有较好预防醉酒和解酒作用，其作用机理可能与其降低血中乙醇含量有关。     

醒酒护肝口服液对小鼠酒精性肝损伤的保护作用简

目的评价醒酒护肝口服液对酒精性肝损伤的保护作用。方法建立小鼠急性酒精肝损伤模型,监测血中乙醇浓度,以评价醒酒护肝口服液对乙醇清除速率的作用;建立小鼠慢性酒精性肝损伤模型,以血液生化指标天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、肝指数及肝组织病理学检查评价醒酒护肝口服液的护肝作用。结果醒酒护肝口服液组小鼠血中乙醇代谢速率加快,浓度降低;药物组均可降低肝损伤小鼠AST、ALT、肝损伤评分值;与模型对照组比较,醒酒护肝口服液组A1月有显著性差异。结论醒酒护肝口服液对酒精性肝损伤有保护作用。     

醒酒浓缩液的药效学研究

目的观测醒酒浓缩液对醉酒小鼠防醉和解酒作用.方法采用醉酒模型并测试小鼠翻正反射消失时间及恢复时间(min),气相色谱检测血中乙醇含量.结果 (1)30mL/kg、40mL/kg醒酒浓缩液对醉酒小鼠具有明显防醉和解酒作用(P<0.05～0.01);(2)醉酒前给小鼠ig醒酒浓缩液,中、高剂量组能明显降低酒后40～120min内血液中乙醇含量(P<0.05～0.01).结论本品具有较好预防醉酒和解酒作用,其作用机理可能与其降低血中乙醇含量有关.     

醒脑静注射液对乙醇所致记忆功能障碍的影响

目的 :观察醒脑静注射液 (Xnji)对乙醇所致记忆障碍的改善作用。方法 :乙醇一次给大鼠和小鼠灌服和连续灌服造成学习记忆功能障碍 ,学习记忆的测试采用Morris水迷宫法 ,电迷宫法和避暗法。结果 :Xnji 1.4 ,0 .7ml·kg-1可预防一次性灌服乙醇所致的大鼠空间辨别障碍 ;Xnji 1,2ml·kg-1可治疗连续灌服乙醇所致的小鼠空间辨别障碍和记忆获得障碍。结论 :Xnji可防治急、慢性乙醇中毒所致的学习记忆功能减退。     

Disulfiram enhances ethanol pharmacological activity and impairs its elimination

Disulfiram or diethyldithiocarbamate (DDC) significantly prolonged ethanol-induced loss of righting reflex in mice. The disappearance of ethanol from blood, and brain was significantly delayed in disulfiram-treated animals, suggesting an impairment in the activity of alcohol dehydrogenase in these animals. DDC, an active metabolite of disulfiram, inhibited mouse liver alcohol dehydrogenase (LADH) in vitro. Pyrazole, a known inhibitor of alcohol dehydrogenase, affected ethanol elimination and ethanol-induced loss of righting reflex in mice in a manner similar to that seen with disulfiram.     

Pharmacological and Metabolic Interactions between Ethanol and Methyl n-Butyl Ketone, Methyl Isobutyl Ketone, Methyl Ethyl Ketone, or Acetone in Mice

Methyl n-butyl ketone (MnBK), methyl isobutyl ketone (MIBK),methyl ethyl ketone (MEK), and acetone are widely used industrialsolvents to which certain groups of workers are exposed. Pharmacologicaland metabolic interactions between these solvents and ethanolwere explored in male CD-1 mice. The effects of these solventson the duration of ethanol-induced loss of righting reflex andon ethanol elimination in mice were studied. The solvents weredissolved in corn oil and injected intraperitoneally 30 mm beforeethanol 4 g/kg ip. The four solvents prolonged significantlythe duration of ethanol-induced loss of righting reflex whengiven in the following doses (m mol/kg): MnBK, 3.75 and 5; MIBK,5; MEK, 5 and 10, acetone, 20 and 40. This prolongation wasdose related and increased as the dose of the solvent was increased.The concentrations of ethanol in blood or brain on return ofthe righting reflex were similar in solvent-treated and controlanimals, with the exception of the group of mice treated with40 mmol/kg acetone in which the ethanol concentrations weresignificantly lower than in control animals. The mean eliminationrate of ethanol was markedly reduced in mice treated with MnBK5 mmol/kg, MEK 15 mmol/ kg, and acetone 40 mmol/kg. All foursolvents reduced the activity of mouse liver alcohol dehy-drogenasein vitro. It is concluded that enhancement of the ethanol-inducedloss of righting reflex by these solvents in mice is well correlatedto reduced elimination rate of ethanol.     

Non-specific prolongation of the effects of general depressants by pyrazole and 4-methylpyrazole

The liver alcohol dehydrogenase inhibitors, pyrazole and 4-methylpyrazole, have been tested for their ability to prolong drug-induced sleep times in mice. Both drugs (at 1 mmol kg-1 i.p.) prolonged the duration of loss of righting reflex following chloral hydrate, pentobarbitone, barbitone, temazepam and halothane, but not diethyl ether. This suggests that the effects of these pyrazoles are not specific to the inhibition of liver alcohol dehydrogenase.     

Inhibition of alcohol dehydrogenase by dimethyl formamide and dimethyl sulfoxide

Dimethyl formamide (DMF) and dimethyl sulfoxide (DMSO) inhibit mouse liver alcohol dehydrogenase (LADH) in vitro. The inhibition is “uncompetitive” with both DMF and DMSO, where both Km and Vmax were changed in the presence of the inhibitor. Both DMF and DMSO prolonged significantly ethanol-induced loss of righting reflex in mice, but not barbital-induced loss of righting reflex.     

Pharmacological and metabolic interactions between ethanol and the dopamine-β-hydroxylase inhibitor FLA 63 in mice

The duration of ethanol-induced loss of righting reflex was significantly prolonged in mice pretreated with the dopamine-β-hydroxylase inhibitor FLA 63. The disappearance of ethanol from blood, brain, liver and kidneys from FLA 63-treated mice was significantly delayed as compared to control mice. In vitro, FLA 63 inhibited the activity of mouse liver alcohol dehydrogenase. These results demonstrate that FLA 63 can alter the disposition of ethanol. Consequently, its pharmacological activity is altered. The interpretation of results from experiments in which FLA 63 is employed with other drugs should not be based solely on its inhibitory action on dopamine-β-hydroxylase.     

Differential response of NADP-linked hepatic aldehyde dehydrogenase toward taurine: implication for behavioural effects of ethanol

The effects of taurine, its initial precursor L-cysteine, and the major metabolite taurocholic acid on two ethanol-mediated responses in rodents were studied. Administration of a single dose of taurocholic acid reduced voluntary intake of a 5% ethanol solution by the rat. In the mouse, taurine had no effect on alcohol drinking or on the central depressant action of ethanol, as measured by the duration of ET-produced loss of the righting reflex. Likewise, taurocholic acid and L-cysteine did not significantly influence the duration of ethanol-narcosis time from control mice. Also studied were the effects of acute and short-term (7 or 10 days) administration of these compounds on hepatic ethanol and acetaldehyde metabolizing enzymes. Short-term administration of an equimolar concentration of taurine enhanced endogenous NADP-linked rat liver aldehyde dehydrogenase (L-ALDH) as contrasted with inhibition of the same enzyme by L-cysteine. Short-term (7 days) treatment with L-cysteine induced rat liver NAD-linked ALDH, but acute (single dose) treatment did not. Taurocholic acid short-term administration caused an induction and an inhibition of endogenous mouse liver alcohol dehydrogenase (L-ADH) and L-ALDH, respectively. The results suggest that taurine does not directly interact with ethanol. However, its major metabolite, taurocholic acid, may cause rapid metabolic conversion of ethanol to acetaldehyde by induction of L-ADH, which is then slowly metabolized due to a concomitant inhibition of L-ALDH. This may cause a build-up of acetaldehyde and thereby produce adverse reactions similar to those resulting from the combination of disulfiram and ethanol.     

Inhibition of mouse liver alcohol dehydrogenase by methyl N-butyl ketone

Methyl N-butyl ketone (MNBK) inhibited the activity of mouse liver alcohol dehydrogenase (LADH) in vitro. Ethanol elimination was reduced in MNBK-treated mice as compared to controls. Ethanol-induced induced loss of righting reflex was significantly prolonged in mice pretreated with MNBK.     

Effects of cyanamide and acetaldehyde accumulation on the locomotor stimulant and sedative effects of ethanol in mice

Ethanol administration induces both locomotor stimulant and sedative effects depending upon blood ethanol concentrations. Recent studies in rats and mice suggest that acetaldehyde, the first product of ethanol metabolism, might be involved in the expression of both the stimulant and the sedative effects of ethanol. A number of studies have used the drug cyanamide in an attempt to clarify the role of acetaldehyde in the behavioral effects of ethanol. The results of such studies are, however, difficult to interpret because cyanamide is an inhibitor of the enzymes catalase and aldehyde dehydrogenase, two enzymes with opposite effects on brain acetaldehyde concentrations. This study was aimed at clarifying the effects of cyanamide on ethanol-induced locomotor stimulant and sedative effects in Swiss mice. The locomotor stimulant effects of ethanol were measured in standard activity boxes, whereas the sedative effects of ethanol were quantified using the loss of righting reflex procedure. Cyanamide prevented the locomotor stimulant effects of 2 g/kg ethanol, although this was mainly due to a potentiation of the inhibitory effects of ethanol as evidenced by a prolongation of ethanol-induced loss of righting reflex. Additionally, 4-methylpyrazole, an inhibitor of the enzyme alcohol dehydrogenase, prevented these effects of cyanamide. It is concluded that in vivo the effects of cyanamide are predominantly due to the inhibition of the enzyme aldehyde dehydrogenase, rather than to its effects on catalase.