Hepatic Alcohol Dehydrogenase Activity Research Articles

Musculus senhousei as a promising source of bioactive peptides protecting against alcohol-induced liver injury.

Alcohol-induced liver injury has become a leading risk for human health, however, effective strategies for the prevention or treatment are still lacking. Hence, the present study explored the potential of Musculus senhousei as a source of hepatoprotective peptides against alcoholic liver injury using in vitro, in vivo and in silico methods. Results indicated that Musculus senhousei peptides (MSP, extracted by simulated gastrointestinal digestion of cooked mussel) exhibited notable antioxidant (ABTS and DPPH assays) and alcohol dehydrogenase (ADH) stabilizing activity in vitro. The ingestion of MSP markedly alleviated alcohol-induced liver injury in mice, as indicated by the decrease of serum transaminases (AST and ALT). In line with in vitro assays, significantly increased hepatic ADH activity and activated antioxidative defense system (GSH, SOD, GSH-Px and CAT) were observed, whereas the oxidative stress (MDA) was decreased. Peptidomic analysis revealed over 6000 peptides with favorable amino acid compositions, and a total of 20 potentially novel peptides with bioactivity and bioavailability were excavated among 746 of the most influential peptides using an in silico strategy. Peptides (i.e. WLPMKL, WLWLPA, RLC and RCL) were further synthesized and validated in vitro to be bioactive. These findings suggest that Musculus senhousei can be an ideal source of bioactive peptides for the prevention of alcoholic liver injury.

Aqueous extract of Laurus nobilis leaf accelerates the alcohol metabolism and prevents liver damage in single-ethanol binge rats.

Excessive alcohol consumption has harmful health effects, including alcohol hangovers and alcohol-related liver disease. Therefore, methods to accelerate the alcohol metabolism are needed. Laurus nobilis is a spice, flavoring agent, and traditional herbal medicine against various diseases. This study examined whether the standardized aqueous extract of L. nobilis leaves (LN) accelerates the alcohol metabolism and protects against liver damage in single-ethanol binge Sprague-Dawley (SD) rats. LN was administered orally to SD rats 1 h before ethanol administration (3 g/kg body weight [BW]) at 100 and 300 mg/kg BW. Blood samples were collected 0.5, 1, 2, and 4 h after ethanol administration. The livers were excised 1 h after ethanol administration to determine the hepatic enzyme activity. The alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the liver tissue were measured. LN decreased the serum ethanol and acetaldehyde levels in ethanol-administered rats. LN increased the hepatic ADH and ALDH activities but decreased the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities in the ethanol-administered rats. In addition, LN inhibited lipid peroxidation and increased the activities of SOD and GPx. LN modulates the mediators of various etiological effects of excessive alcohol consumption and enhances the alcohol metabolism and antioxidant activity, making it a potential candidate for hangover treatments.

Hepatoprotective effect of clam (Corbicula fluminea) protein hydrolysate on alcohol-induced liver injury in mice and partial identification of a hepatoprotective peptide from the hydrolysate

In the current research, edible meat of freshwater clam Corbicula fluminea was subjected to enzymatic peptide extraction using animal protease. The clam protein hydrolysate (CPH) contained 45.78% essential amino acids and 44.97% hydrophobic amino acids and showed high alcohol dehydrogenase (ADH) activation in vitro. Four fractions were divided from CPH by ultrafiltration and further investigated for their hepatoprotective effects on alcohol-induced injury in mice. The 2.5-5 kDa fraction (CPH-3) showed the best effect for preventing hepatic damage caused by alcohol, as revealed by reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) activities and hepatic malondialdehyde (MDA) level, the marked decrease in the hepatic triglyceride (TG) contents, and the enhanced hepatic ADH, aldehyde dehydrogenase (ALDH), and glutathione (GSH) activities. Furthermore, histopathology of CPH-3-treated mice showed less hepatic tissue damage compared to alcohol- or other CPHs-treated mice. Hence, CPH-3 was further purified by consecutive chromatographic techniques with gel filtration and reverse-phase high-performance liquid chromatography. One hepatoprotective peptide, KKLAGFLRYYS (1330.68 Da), was identified by LC-MS/MS, which exhibited strong ADH activation activity. Results suggested that CPH could be a potential nutraceutical for facilitating alcohol metabolism and preventing or ameliorating early liver injury induced by acute alcohol exposure and that the peptide KKLAGFLRYYS is one of the main bioactive components in CPH.

Role of first aid in the management of acute alcohol intoxication: a narrative review.

Acute alcohol intoxication is actually a common admission cause in the Emergency Department and represents an increasing public health burden, in particular among adolescents. It involves possible and significant illness and injury, which can quickly get worse and may need to be managed in the emergency room. We conducted a narrative review of the literature regarding the effectiveness of first aid role of the Emergency Department setting. This review included eighteen studies about alcohol intoxication management in the Emergency Department; most of all highlights the emerging phenomenon in Europe and around the world of acute alcohol intoxication management in first aid. The treatment of acute alcohol intoxication depends on general clinical conditions of the patient, vital signs, hemodynamic stability, cognitive state, alcohol-related complications, which are closely related to the blood alcohol concentration. At the same time, symptoms could be extremely variable due to individual differences in alcohol metabolism. In case of mild-moderate intoxication (blood alcohol concentration < 1 g/L), no drugs are necessary. In case of severe intoxication (blood alcohol concentration > 1 g/L), it is necessary to support with intravenous fluids, treat hypoglycemia, hypotension, hypothermia and electrolyte imbalance, administer complex B and C vitamins and accelerate alcohol elimination from blood with metadoxine. Unlike adults, adolescents are more exposed to the toxic effect of alcohol (because of their immature hepatic alcohol dehydrogenase activity), and then, acute alcohol-related complications are more frequent and dangerous in young people than in adult population. In many cases, patients affected by acute alcohol intoxication referring to an Emergency Department have mild-moderate transitory symptoms that do not require the use of drugs; they can benefit from a clinical observation, with a clinical course often completed within 24 hours with a favorable outcome. Clinical observation with vital signs control is necessary also to evaluate the possible development of the alcohol withdrawal syndrome (that involves a specific treatment) and to evaluate also possible pathological complications of the organism, above all acute liver damage. Patients affected by acute alcohol intoxication are the best candidates to apply the rules of the Temporary Observation Unit in the Emergency Department, because of a clinical course often completed within 24 hours, a favorable outcome and without the need for hospitalization. In many cases, hospitalization could be not necessary, but the patient affected by Alcohol Use Disorder must be referred to an Alcohol Addiction Unit for the follow-up, to reduce the risk of alcohol relapse and complications related to alcohol abuse, and financial costs of hospitalization.

흰쥐에서 어성초 열수 추출물을 포함한 혼합물의 숙취해소 효과

This study was performed to investigate the ameliorating effect of a mixture of extracts from Houttuynia cordata Thunb, Nelumbo nucifera G. (leaf), and Camellia sinensis (seed) (MIX) on acute ethanol-induced hangover in Sprague-Dawley rats. Plasma ethanol and acetaldehyde levels in MIX-treated rats significantly decreased at 3 h and 5 h after acute ethanol administration (25%, 3 g/kg body weight/d) as compared to ethanol-treated rats. Hepatic alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were significantly higher in MIXtreated rats than in ethanol-treated rats. MIX exhibited high ADH and ALDH activities on direct assays using S9 rat liver fraction for ethanol metabolic enzymes clearance action. These results suggest that MIX could alleviate ethanol-induced hangover symptoms by elevating activities related to hepatic ethanol-metabolizing enzymes against ethanol induced metabolites, and MIX should be further developed to be a new anti-hangover material.

Diet Supplementation with Allicin Protects against Alcoholic Fatty Liver Disease in Mice by Improving Anti-inflammation and Antioxidative Functions.

This study investigated the liver-protective effects of allicin, an active compound in fresh garlic, against alcoholic fatty liver disease (AFLD) and liver inflammation. Its effects were investigated in an AFLD model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Allicin (5 and 20 mg/kg bw/day) was orally administered daily in the AFLD mice for 4 weeks. The results indicate that allicin promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels (p < 0.05) in the plasma, which are key indicators of liver damage. Allicin reduced fat accumulation, increased glutathione and catalase levels, and decreased microsomal protein cytochrome P450 2E1 (CYP2E1) expression (p < 0.05) in the livers of the AFLD mice. Furthermore, allicin supplementation significantly decreased the levels of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and suppressed the expression of sterol regulatory element-binding protein-1 (SREBP-1) (p < 0.05). Additionally, it improved the hepatic alcohol dehydrogenase (ADH) activity (p < 0.05). Collectively, these findings demonstrate that allicin attenuates liver oxidative stress and inflammation.

Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes

Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol–drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0.1 M sodium phosphate at pH 7.5 and 25 °C containing 0.5 mM NAD+. The organ simulations reveal that the ADH activities in mucosae of the stomach, duodenum and jejunum with ADH1C*1/*1 genotype are less than 1%, respectively, that of the ADH1B*1/*1–ADH1C*1/*1 liver at 1–200 mM ethanol, indicating that liver is major site of the FPM. The apparent hepatic KM and Vmax for ethanol oxidation are simulated to be 0.093 ± 0.019 mM and 4.0 ± 0.1 mmol/min, respectively. At 95% clearance in liver, the logarithmic average sinusoidal ethanol concentration is determined to be 0.80 mM in accordance with the flow-limited gradient perfusion model. The organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of ADH1B*1/*1 hepatic ADH activity at 2–20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30–31% of the ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol FPM in these allelotypes. The result provides systematic evaluations and predictions by computer simulation on potential ethanol FPM in target tissues and hepatic ethanol–drug interactions in the context of tissue ADH isozymes.

Impact of Dyrk1A level on alcohol metabolism

Alcoholic liver diseases arise from complex phenotypes involving many genetic factors. It is quite common to find hyperhomocysteinemia in chronic alcoholic liver diseases, mainly due to deregulation of hepatic homocysteine metabolism. Dyrk1A, involved in homocysteine metabolism at different crossroads, is decreased in liver of hyperhomocysteinemic mice. Here, we hypothesized that Dyrk1A contributes to alcohol-induced hepatic impairment in mice. Control, hyperhomocysteinemic and mice overexpressing Dyrk1A were fed using a Lieber-DeCarli liquid diet with or without ethanol (5% v/v ethanol) for one month, and liver histological examination and liver biochemical function tests were performed. Plasma alanine aminotransferase and homocysteine levels were significantly decreased in mice overexpressing Dyrk1A compared to control mice with or without alcohol administration. On the contrary, the mean plasma alanine aminotransferase and homocysteine levels were significantly higher in hyperhomocysteinemic mice than that of control mice after alcohol administration. Paraoxonase 1 and CYP2E1, two phase I xenobiotic metabolizing enzymes, were found increased in the three groups of mice after alcohol administration. However, NQO1, a phase II enzyme, was only found increased in hyperhomocysteinemic mice after alcohol exposure, suggesting a greater effect of alcohol in liver of hyperhomocysteinemic mice. We observed positive correlations between hepatic alcohol dehydrogenase activity, Dyrk1A and ADH4 protein levels. Importantly, a deleterious effect of alcohol consumption on hepatic Dyrk1A protein level was found. Our study reveals on the one hand a role of Dyrk1A in ethanol metabolism and on the other hand a deleterious effect of alcohol administration on hepatic Dyrk1A level.

Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant-negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking. To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated. The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5-6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes. Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.

Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference in mice.

Stressful life events are causally linked with alcohol use disorders (AUDs), providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen) littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

Green Tea Extract (Camellia sinensis) Fermented byLactobacillus fermentumAttenuates Alcohol-Induced Liver Damage

Here, the impact of an extract derived from green tea (Camellia sinensis) and fermentation with Lactobacilli fermentum strain OCS19 was explored with acute alcohol-induced liver damage. The study employed the HepG2 hepatic cell line and an in vivo murine model of liver damage. L. fermentum-fermented green tea extract (FGTE) was found to possess pronounced alcohol metabolizing enzyme activity. It significantly enhanced the cell viability of HepG2 cells following of them exposure, to ethanol (p<0.05) as compared with an extract derived from Hovenia dulcis, a positive control that is known for its action as an alcohol antagonist. Our in vivo studies indicated that prior administration of FGTE to alcohol-exposed mice significantly prevented subsequent increases in blood alcohol concentration (p<0.05), in addition to the induction of serum alanine aminotransferase (ALT) and triglycerides (p<0.05). Furthermore, the activity of hepatic alcohol dehydrogenase (ADH) and its mRNA expression level both increased in the livers of mice treated with FGTE, similarly to the H. dulcis-treated group. Taken together, these results may suggest that green tea extract coupled with L. fermentum fermentation attenuates the risk of ethanol-induced liver damage.

β-catenin is essential for ethanol metabolism and protection against alcohol-mediated liver steatosis in mice.

The liver plays a central role in ethanol metabolism, and oxidative stress is implicated in alcohol-mediated liver injury. β-Catenin regulates hepatic metabolic zonation and adaptive response to oxidative stress. We hypothesized that β-catenin regulates the hepatic response to ethanol ingestion. Female liver-specific β-catenin knockout (KO) mice and wild-type (WT) littermates were fed the Lieber-Decarli liquid diet (5% ethanol) in a pairwise fashion. Liver histology, biochemistry, and gene-expression studies were performed. Plasma alcohol and ammonia levels were measured using standard assays. Ethanol-fed (EtOH) KO mice exhibited systemic toxicity and early mortality. KO mice exhibited severe macrovesicular steatosis and 5 to 6-fold higher serum alanine aminotransferase and aspartate aminotransferase levels. KO mice had a modest increase in hepatic oxidative stress, lower expression of mitochondrial superoxide dismutase (SOD2), and lower citrate synthase activity, the first step in the tricarboxylic acid cycle. N-Acetylcysteine did not prevent ethanol-induced mortality in KO mice. In WT livers, β-catenin was found to coprecipitate with forkhead box O3, the upstream regulator of SOD2. Hepatic alcohol dehydrogenase and aldehyde dehydrogenase activities and expression were lower in KO mice. Hepatic cytochrome P450 2E1 protein levels were up-regulated in EtOH WT mice, but were nearly undetectable in KO mice. These changes in ethanol-metabolizing enzymes were associated with 30-fold higher blood alcohol levels in KO mice. β-Catenin is essential for hepatic ethanol metabolism and plays a protective role in alcohol-mediated liver steatosis. Our results strongly suggest that integration of these functions by β-catenin is critical for adaptation to ethanol ingestion in vivo.

Comparative Study of the Hepatoprotective Efficacy of Artemisia iwayomogi and Artemisia capillaris on Ethanol‐Administered Mice

We compared the effects of ethylacetate extracts from Artemisia iwayomogi (AIE) and Artemisia capillaris (ACE) on ethanol-induced hepatic injury in mice. Ethanol (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 wk. AIE or ACE was provided in the diet (0.05 g/100 g diet). AIE and ACE did not affect hepatic alcohol dehydrogenase activity but did significantly inhibit cytochrome P450 2E1 activity. Hepatic acetaldehyde dehydrogenase 2 activity significantly increased in the AIE group compared to the control group. AIE caused a significant decrease in plasma acetaldehyde levels and aspartate transaminase and lactate dehydrogenase activities, whereas ACE slightly decreased these values compared to the control. Hepatic catalase activity and glutathione levels were significantly increased by AIE and ACE supplements, whereas glutathione peroxidase activity was higher only in the AIE group compared to the control group. AIE and ACE supplements significantly lowered the plasma cholesterol concentration and increased the HDL-cholesterol/total cholesterol ratio compared to the control group. Compared to the control, both AIE and ACE groups showed a significant decrease in hepatic triglyceride levels and an increase in fecal triglyceride excretion simultaneous with inhibition hepatic activities of fatty acid synthase, phosphatidate phosphohyrolase, fatty acid β-oxidation, and carnitine palmitoyltransferase. AIE significantly lowered hepatic cholesterol levels and increased fecal cholesterol levels compared to the control. These results indicate that AIE and ACE exhibit hepatoprotective and hypolipidemic properties by enhancing hepatic alcohol, antioxidant, and lipid metabolism. AIE seemed to have more potent hepatoprotective effects than ACE.

오이 발효음료가 만성적으로 에탄올을 급여한 흰쥐의 에탄올 대사와 항산화방어계에 미치는 영향

Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r

Protective effects of garlic oil on n-hexane-induced neurotoxicity in rats via inhibition of hepatic alcohol dehydrogenase activity

To study the protective effects of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane. Male Wistar rats were randomly divided into four groups (10 rats in each group): the control, the n-hexane treatment (2000 mg/kg), the low dose GO, and the high dose GO groups. The rats in the low and high doses of GO groups were pretreated with GO (40 and 80 mg/kg) before exposure to n-hexane (2000 mg/ kg), while the animals of the n-hexane treatment group were given normal saline and then 2000 mg/ kg n-hexane. The rats were exposed to GO and n-hexane 6 times a week for 10 weeks. The gait scores and staying time on the rotating rod for all rats were detected every two weeks. The rats were sacrificed at the end of ten weeks, then the levels of alcohol dehydrogenase (ADH), maleic dialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase(GSH-Px), total antioxidation capacity(T-AOC) and the ability of inhibition of *OH in livers were examined. The gait scores increased significantly and the time staying on the rotating rod obviously decreased in rats of n-hexane treatment group, as compared with control group (P < 0.05 or P < 0.01). In the hepatic tissues of n-hexane group, the levels of MDA and ADH significantly increased, the activities of GSH-Px, T-AOC and the ability of inhibition of *OH obviously decreased, as compared to control group (P < 0.05 or P < 0.01). In 2 GO groups, the gait scores and the staying time on the rotating rod were significantly improved, the levels of MDA and ADH significantly decreased, the activities of GSH-Px, T-AOC and the ability of inhibition of *OH obviously increased, as compared with n-hexane group (P < 0.05 or P < 0.01 ). ADH could play an important role in the protective effects induced by garlic oil on the peripheral nerve injuries produced by n-hexane.

Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase

Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p < 0.01), but DEG concentrations in the blood, liver and kidneys were lower. Hepatic alcohol dehydrogenase (ADH) activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.

The pharmacological potential ofSorbus commixtacortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated rats

The effect of Sorbus commixta cortex, a traditional herbal medicine used for the treatment of bronchitis, gastritis and dropsy, on blood alcohol concentration (BAC) and hepatic lipid peroxidation was examined in acute alcohol-treated rats. A 30-min pretreatment with a methanol extract of S. commixta cortex (SC) at concentrations higher than 200 mg kg(-1) resulted in a significant decrease in BAC and the ethyl acetate fraction (SE) of the extract showed the highest potency, with a maximum of a 46% decrease at 150 mg kg(-1) 2 h after alcohol administration (3.0 g kg(-1)) compared with the control group (P < 0.005). The rapid reduction in BAC did not appear to be due to the protection or activation of hepatic alcohol dehydrogenase (ADH) activity by SE. Hepatic malondialdehyde (MDA) levels were significantly increased by acute alcohol administration within 6 h, although pretreatment with the SE caused a significant decrease in MDA levels compared with alcohol treatment alone. Hepatic glutathione (GSH) levels and superoxide dismutase (SOD) activity remained unchanged by alcohol, SE alone or by the combined treatment of alcohol and SE. However, catalase activity was significantly reduced by acute alcohol administration and pretreatment with the SE led to significant protection of its activity. These results suggest that pretreatment with SE reduces hepatic lipid peroxidation by decreasing the bioavailability of alcohol and its oxidative metabolites, such as H2O2, at least partly, through the protection of hepatic catalase in acute alcohol-treated rats.

눈꽃동충하초 물추출물이 흰쥐의 알코올대사에 미치는 영향

본 연구에서는 눈꽃동충하초 물추출물이 알코올 대사에 미치는 효과를 동물실험을 통하여 살펴보았다. 알코올과 그대사산물인 아세트알데히드의 혈중 농도를 측정한 결과, 눈꽃동충하초 물추출물의 경구투여는 흰쥐의 혈중 알코올 농도에는 영향을 미치지 않았으나, 3, 6, 9시간째의 혈중 아세트알데히드 농도를 유의적으로 감소시켰다. 특히 100 ㎎/㎏ 농도의 눈꽃동충하초 물추출물 투여 시 혈중 아세트알데히드의 농도-시간 곡선하 면적에서 유의적인 감소를 보였다. 반면에 알코올 투여 후 9시간째 측정한 간의 알코올 탈수소효소, 알데히드 탈수소효소, MEOS의 활성은 눈꽃동충하초물추출물 투여에 따른 변화를 보이지 않았다. 종합적으로 눈꽃동충하초 물추출물은 혈중 알코올 농도에는 영향을 미치지 않으나 혈중 아세트알데히드 농도를 감소시키는 것으로 보인다. 눈꽃동충하초 물추출물이 혈중 아세트알데히드 수준을 낮추는 작용기전과 관련하여, 경시적인 알코올대사 효소활성의 변화와 간 손상 관련 지표 조사 등에 관한 추가적인 연구가 필요할 것으로 사료된다.

차나무(Camellia sinensis) 추출물이 아급성 알코올 투여 마우스의 항산화 및 알코올 분해 효소 활성에 미치는 영향

This study was conducted to investigate the effects of four kinds of tea (Camellia sinensis) extracts on the antioxidant defense systems as well as the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in ethanol administered ICR mice. According to the results, treatment with puerh tea significantly increased the superoxide dismutase activity and glutathion reductase activity in liver. In addition, the group treated with oolong tea exhibited higher superoxide dismutase activity and glutathion reductase activity in serum than those of puerh tea, green tea and black tea treated groups. The oolong tea and puerh tea also reduced malondealdehyde contents in both liver and serum. These results suggested that puerh tea and oolong tea were the most effective against alcohol?induced oxidative damage among the Camellia sinensis teas. On the other hand, in the measurement of alcohol break?down enzyme activities, the group treated with green tea exhibited the highest hepatic ADH and ALDH activities, suggesting that the group treated with green tea might be useful for alcohol down?regulation.

Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol

Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ-primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs.