Ethanol-induced Liver Toxicity Research Articles

Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity.

Schizandrae Fructus (SF), fruits of Schisandra chinensis (Turcz.) Baill. and Hoveniae Semen cum Fructus (HSCF), the dried peduncle of Hovenia dulcis Thunb., have long been used for alcohol detoxification in the traditional medicine of Korea and China. In the current study, we aimed to evaluate the potential synergistic hepatoprotective effect of a combination mixture (MSH) comprising fermented SF pomace (fSFP) and HSCF hot water extracts at a 1:1 (w:w) ratio against ethanol-induced liver toxicity. Subacute ethanol-mediated hepatotoxicity was induced by the oral administration of ethanol (5 g/kg) in C57BL/6J mice once daily for 14 consecutive days. One hour after each ethanol administration, MSH (50, 100, and 200 mg/kg) was also orally administered daily. MSH administration significantly reduced the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Histological observation indicated that MSH administration synergistically and significantly decreased the fatty changed region of hepatic parenchyma and the formation of lipid droplet in hepatocytes. Moreover, MSH significantly attenuated the hepatic triglyceride accumulation through reducing lipogenesis genes expression and increasing fatty acid oxidation genes expression. In addition, MSH significantly inhibited protein nitrosylation and lipid peroxidation by lowering cytochrome P450 2E1 enzyme activity and restoring the glutathione level, superoxide dismutase and catalase activity in liver. Furthermore, MSH synergistically decreased the mRNA level of tumor necrosis factor-α in the hepatic tissue. These findings indicate that MSH has potential for preventing alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress, and inflammation.

Hepatoprotective and Antioxidant Potential of Phenolics-Enriched Fraction of Anogeissus acuminata Leaf against Alcohol-Induced Hepatotoxicity in Rats.

Anogeissus acuminata is used to treat wounds, diarrhoea, dysentery, and skin ailments. However, its hepatoprotective effect against ethanol-induced liver damage is yet to be reported. The phenolic-enriched ethyl acetate fraction of Anogeissus acuminata (AAE) was evaluated for hepatoprotective activity against ethanol-induced liver toxicity in rats. The intoxicated animals were treated with a phenolic-rich fraction of Anogeissus acuminata (AAE) (100 and 200 mg/kg) and silymarin (100 mg/kg). The antioxidant activity of AAE was analysed. Biochemical markers (ALT, AST, ALP, GGT, and TBL) for liver injury in ethanol-administered animals resulted in higher levels of key serum biochemical injury markers, as evidenced by increased levels of ALT (127.24 ± 3.95), AST (189.54 ± 7.56), ALP (263.88 ± 12.96), GGT (91.65 ± 3.96), and TBL (2.85 ± 0.12) compared to Group I ALT (38.67 ± 3.84), AST (64.45 ± 5.97), GGT (38.67 ± 3.84), and TBL (0.53 ± 064) (p < 0.05). AAE administration decreased serum biochemical liver injury markers as manifested in Group III animals’ ALT (79.56 ± 5.16), AST (151.76 ± 6.16), ALP (184.67 ± 10.12), GGT (68.24 ± 4.05), TBL (1.66 ± 0.082) (p < 0.05), and Group IV ALT (55.54 ± 4.35), AST (78.79 ± 4.88), ALP (81.96 ± 9.43), GGT (47.32 ± 2.95), TBL (0.74 ± 0.075) (p < 0.05). Group IV exhibited the most significant reduction in serum biochemical markers as compared to Group III (p < 0.05) and close to silymarin-treated Group V ALT (44.42 ± 3.15), AST (74.45 ± 5.75), ALP (67.32 ± 9.14), GGT (42.43 ± 2.54), TBL (0.634 ± 0.077). Gene expression indices and histoarchitecture were evaluated to demonstrate the potential of AAE. The bioactive fraction of Anogeissus acuminata was rich in phenolics and flavonoid content. GC–MS analysis identified gallic acid, palmitic acid, cis-10-heptadecenoic acid, 9-octadecenoic acid, epigallocatechin, 2,5-dihydroxyacetophenone, and catechin. Oral administration of AAE (100 and 200 mg/kg) lowered the elevated levels of the biochemical markers and interleukin, and enhanced the level of enzymatic antioxidant. It also downregulated the expression level of proapoptotic genes and upregulated the expression level of the antiapoptotic gene along with improved liver histopathology.

Myricetin (3,3',4',5,5',7-hexahydroxyflavone) prevents ethanol-induced biochemical and inflammatory damage in the liver of Wistar rats.

Purpose:The current investigation was carried out to evaluate the efficacy of myricetin in ethanol-induced liver toxicity in Wistar rats.Research Design:Twenty-four rats were randomly divided into four groups with six animals per group. Group-I animals were administered with vehicle (distilled water), Group II, III, and IV were treated orally with sequential (per week) increase in the dose of ethanol (5, 8, 10, and 12 g/kg b wt per week in each group) for 28 days. Myricetin was treated orally to Group-III and IV animals at the respective doses of 25 mg/kg b wt. and 50 mg/kg b wt.Results:Our results showed that myricetin prevented hepatotoxicity by modulating the production of free radicals, ethanol metabolizing enzymes, and inflammatory markers in vivo. Myricetin also helped maintain lipid membrane integrity, oxidant-antioxidant status, and histoarchitecture. Ethanol administration caused elevation in XO, ADH, and CYP2E1 in hepatic tissue, which significantly normalized with myricetin administration. After ethanol administration, there was a steep increase in the hepatotoxicity biomarkers, including ALT, MDA, and AST. The level of cytotoxicity marker LDH also increased after ethanol administration; myricetin administration decreased the level of all these markers. Moreover, myricetin treatment also reduced ethanol-induced inflammatory markers such as NF-κB and IL-6.Conclusion:Findings from the current study demonstrate that myricetin administration prevents alcohol-induced hepatic injury by influencing the metabolism of ethanol, inhibiting oxidative stress, maintaining lipid profile, and suppressing inflammatory markers.

Voacanga grandifolia (Miq.) Rolfe protects against alcohol-induced liver toxicity in rats

Objective: To evaluate the ethanol extract of Voacanga grandifolia for hepatoprotective and antioxidant potential against ethanolinduced liver toxicity in rats.Methods: Sprague-Dawley rats were administered ethanol (7 g/kg) and then treated with 100 and 200 mg/kg of Voacanga grandifolia extract. The phytochemical constituents and antioxidant potential of Voacanga grandifolia extract were evaluated by GC-MS and in vitro antioxidant assays. Biochemical indicators for liver damage and proapoptotic and antiapoptotic gene expression were determined using biochemical kits, ELISA, and qRT-PCR, respectively. Additionally, histopathological study of the liver was performed.Results: GC-MS identified propanoic acid, meso-erythritol, D-pinitol, myo-inositol, and hexadecanoic acid in Voacanga grandifolia extract. Voacanga grandifolia extract (100 and 200 mg/kg) increased the concentration of enzymatic antioxidants while diminishing the levels of inflammatory cytokines and biochemical indicators. qRT-PCR assay showed that Voacanga grandifolia extracts upregulated antiapoptotic gene expression while downregulating pro-apoptotic gene expression. Furthermore, the plant extract improved the hepatic architecture of ethanol-intoxicated rats.Conclusions: Voacanga grandifolia extract demonstrates hepatoprotective activity against alcohol-induced liver injury in rats and could be a potential hepatoprotective agent.

Antioxidant and Hepatoprotective Activity of Aerides odorata Lour. on Alcohol Induced Liver Damage in Rats

Natural products have been playing a vital role in protection against different diseases since ancient times. Many medicinal plants are still unexplored about their medicinal values scientifically, but they are still used in traditional medicine. The current study was aimed to explore and evaluate the phytochemical constituents, antioxidant activity against different free radicals with in vitro methods and in vivo methods using albino Wistar rats and hepatoprotective activity against ethanol-induced liver toxicity. The extracts of Aerides odorata show sterols, terpenoids, glycosides, saponins, flavonoids, tannins, phenols, alkaloids, quinones and the absence of amino acids and oils. The hydroalcoholic extract had showed presence of more phenolic and alkaloid contents compared to ethyl acetate and hexane extracts of Aerides odorata. The extracts of Aerides odorata had shown antioxidant potentiality in both in vitro and in vivo studies. The extracts had more inhibition in reducing 2,2-diphenyl-1-picrylhydrazyl and almost the same potentiality in altering antioxidant enzymes levels. The extracts of Aerides odorata had shown concentration-dependent hepatoprotective activity. However, it is moderate as compared with the standard drug Liv 52. The hydroalcoholic extracts had more activity compared to ethyl acetate extract. The activity is more in the reduction of free radicals but is lower in the reduction of hepatoprotection. The compound in Aerides odorata may act synergistically or individually in controlling both activities. Further studies are worthful in the evaluation of different biological activities and the isolation of individual bioactive compounds.

Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats.

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Hepatoprotective potential of Dendropanax morbifera leaf extracts on ethanol-induced liver toxicity in Sprague-Dawley rats

This study investigated the preventive effect of Dendropanax morbifera leaf extracts (DMLEs) drew out with water, 30, 50 and 70% ethanol against alcohol-induced hepatotoxicity in vitro and vivo. The 3-(4,5-dimethylthiazol-2-yl)-2,5-dipenyltetrazolium bromide (MTT) assay was performed to assess cytotoxic activity of DMLEs, and the half-maximal inhibitory concentration (IC50) ranged between 1.11 and 2.08 mg/mL on Hep3B cells. In preventing ethanol-induced-hepatotoxicity on Hep3B cells, 30 and 50% ethanol DMLEs were significantly effective compared to the 5% ethanol treatment control. In addition, the 30% ethanol DMLE was orally provided to rats 30 min prior to the administration of ethanol (3 mL/kg body weight). At 1, 3 and 5 h after ethanol treatment, the plasma levels of ethanol and acetaldehyde were determined. The 30% ethanol DMLE effectively decreased the plasma ethanol levels during 5 h but increased the plasma acetaldehyde levels until 3 h and then significantly decreased at 5 h, as compared to the control. These results indicate that the 30% ethanol DMLE possesses a potent preventive effect against ethanol-induced liver toxicity in Sprague-Dawley rats.

Hepatoprotective Activity of Acampe praemorsa

Introduction: Liver is one of major functional organ in body, its damage can alter body metabolisms and other organs’ function. So, it is very important to maintain the healthy liver. Now a days, different chemicals and inadequate use of medicines are causing liver impairments including alcohol consumption. There is a need to identify safe hepatoprotective drugs against liver diseases from different natural resources including medicinal plants. Several medicinal plants have been using in traditional medicines against several diseases including liver disease and many of them are not scientifically proven. So, the current study was aimed to evaluate hepatoprotective nature of Acampe praemorsa.&#x0D; Methodology: The hepatoprotective activity of A. praemorsa was carried on ethanol-induced liver toxicity on albino wistar rats by evaluating the levels of liver biomarker enzymes such as aspartate aminotransferase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP), Total protein (T.ptn), and Total bilirubin (T.Bil).&#x0D; Results: The extracts of Acampe praemorsa were found to be safe at different doses as there were no mortality and physio-psychological changes observed in toxicity study. The extracts of Acampe praemorsa has showed dose dependent hepatoprotective activity on controlling the altered liver biomarker enzymes when compared along with standard drug Liv 52. The hydroalcoholic extract showed better activity compared to ethyl acetate extracts. The percentage protection on liver biomarker enzymes levels of hydro-alcoholic extract at 100, 200, and 400 mg/kg on AST, ALT, ALP, T.ptn, and T.Bil was found to be 62.72%, 60.06%, 61.77%, 63.96% and 58.58% respectively.&#x0D; Conclusion: The results of recent study support traditional medicinal use of Acampe praemorsa and provides the information about its’ hepatoprotective nature. The hepatoprotective activity of A. praemorsa was definitely due to presence of different phytochemical compounds in it as it was compared with Liv 52 which was also an herbal drug.

Possible protective role of punicalagin on oxidative stress, inflammation and genotoxicity in ethanol-induced liver toxicity

Possible protective role of punicalagin on oxidative stress, inflammation and genotoxicity in ethanol-induced liver toxicity

Protective effect of ethanolic extract of Actinoscirpus grossus tubers against ethanol induced liver toxicity in albino rats

Liver detoxifies majority of chemicals and plays an important role in the maintenance of homeostasis of the body. In the recent years due to overwhelming use of drugs and alcohol there is an increased incidence of liver toxicities. The tubers of Actinoscirpus grossus are used in liver disease as a liver tonic in folklore medicine; However, there is no experimental basis for its therapeutic use. Hence the present study was conducted to evaluate the hepatoprotective potentials of ethanolic extract of Actinoscirpus grossus tubers in ethanol induced hepatotoxicity in albino rats. Daily administration of 20% ethanol v/v p.o. at a dose of 5 g/kg for 30 consecutive days caused significant liver toxicity and there after maintained for 15 consecutive days with normal rat pellet and water ad libitum. The treatment groups were administered with group specific drugs for 15 consecutive days after 30 days of ethanol administration and control group rats were maintained for 15 consecutive days with normal rat pellet and water ad libitum. Liver toxicity was assessed on 45th day by estimating biochemical, histological and antioxidant level. Daily administration of 20% ethanol significantly increased liver enzymes and caused oxidative stress by increase in the lipid peroxidation and reduction in the catalase and glutathione peroxidase activity in liver homogenate. The histopathological examination revealed micro vesicular and macro vesicular fatty changes predominantly with mild periportal inflammation, cell infiltrate and areas of mild dilatation of sinusoids with ballooning degeneration of hepatocytes. Treatment with ethanolic extract of A. grossus tuber significantly restored the liver enzymes especially SGOT and attenuated elevated lipid peroxidation and restored catalase and glutathione peroxidase activity. The histopathological changes revealed significant reduction in the hepatocyte ballooning portal fibrosis. Thus, tubers of A. grossus plant may serve as reservoir of natural products having diverse functions and could be utilised as a potent hepatoprotective agent.

Carvacrol inhibits cytochrome P450 and protects against binge alcohol-induced liver toxicity

Alcoholism is a serious addiction that can lead to various health complications such as liver fibrosis, steatosis, and cirrhosis. Carvacrol is present in many plant-based essential oils and used as a preservative in the food industry. In this study, we have investigated the hepatoprotective role of carvacrol against ethanol-induced liver toxicity in mice. To determine the effect of carvacrol on liver injury parameters, 5 doses of 50% ethanol (10 mL/kg body weight) were orally administered every 12 h for inducing the hepatotoxicity in experimental mice. Interestingly, carvacrol pre-treatment (50 and 100 mg/kg) reversed the ethanol-induced effects on liver function, antioxidant markers, matrix metalloproteinases activities, and histological changes. Moreover, carvacrol binds to the active pocket of cytochrome P450 (Cyt P450) and inhibits its expression. Thus, our finding suggests carvacrol can be used as an adjuvant for the amelioration of alcohol-induced hepatotoxicity.

Evaluation of Hepatoprotective activity of Eriocaulon quinquangulare in vitro using porcine liver slices against ethanol induced liver toxicity and free radical scavenging capacity.

BackgroundProduction of reactive oxygen species is a common cause in alcohol induced liver diseases. Decoction prepared from the whole plant of Eriocaulon quinquingulare is prescribed to treat liver disorders. The aim of this study was to investigate the hepatoprotective activity and antioxidant capacity of the water extract of E. quinquangulare in vitro.MethodThe aqueous extract of the whole plant of E. quinquangulare (AEQ) was investigated for its phytochemical constituents, antioxidant and membrane stabilization properties in-vitro. The antioxidant activities of AEQ were investigated using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical, nitric oxide scavenging and ferric reducing antioxidant power (FRAP) assays. Membrane stabilizing effect of the extract was determined by hypotonic solution induced human erythrocyte hemolytic assay (HEHA). Further, hepatoprotective activity against ethanol induced hepatotoxicity was carried out using porcine liver slices.ResultsThe total phenolics and flavonoids were 10.3 ± 1.6 w/w % gallic acid equivalents and 45.6 ± 3.8 w/w % (−)-epigallocatechin gallate equivalents respectively. The values of EC50 for DPPH, hydroxyl radical and nitric oxide scavenging assays were 37.2 ± 1.7 μg/ml, 170.5 ± 6.6 μg/ml and 31.8 ± 2.2 μg/ml respectively. The reducing capability of AEQ was 6.9 ± 0.2 w/w % L-ascorbic acid equivalents in the FRAP assay. For hypotonic solution induced HEHA, the IC50 was 1.79 ± 0.04 mg/ml. A significant decrease (p < 0.05) was observed in ALT, AST and LDH release from the liver slices treated with AEQ compared to the ethanol treated liver slices. A significant reduction in lipid peroxidation (p < 0.05) was also observed in liver slices treated with the plant extract compared to that of the ethanol treated liver slices.ConclusionsThe results suggest AEQ possess hepatoprotective activity against ethanol induced liver toxicity of porcine liver slices which can be attributed to antioxidant properties and membrane stabilizing effects caused by the plant material.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1044-x) contains supplementary material, which is available to authorized users.

PTH-094 Are megamitochondria a cellular survival strategy for ethanol-induced liver toxicity?

Introduction A characteristic histological feature of alcoholic liver disease (ALD), known since the 1970s, is the presence of megamitochondria (MM) in hepatocytes. In a recent study conducted in more than 100 patients, the presence of MM was associated with a lower risk of death within 90 days.1Mitochondria are dynamic organelles and their shape is intimately involved with their function, under physiological conditions the changes in mitochondrial morphology are regulated by mitochondrial-shaping proteins (MSP). However, the mechanisms driving MM formation, their role, function and involvement in the pathogenesis of ALD is currently unknown, which is the aim of this study. Method Human precision cut liver slices (PCLS) and hepatoma cells VL-17A (positive for ADH/CYP2E1) were cultured with EtOH alone or in combination with FFA, to induce hepatotoxicity. Cell viability was evaluated by FACS (AnnexinV/PI positive cells) or ATP quantification. Post-treatment, changes in the mitochondrial shape were assessed by confocal and electron microscopy; MSP expression and activation was also analysed by Western blot on isolated mitochondria. Additionally, mitochondrial functionality was evaluated in intact cells using the Seahorse Bioscience analyser. Changes in inflammatory cytokine production were assessed by Cytokine Bead Array. Results The toxic effect of EtOH (+/-FFA) was confirmed by an increase in the percentage of dead cells or a reduction in ATP levels. Cells that survived the toxic insult showed a dramatically increased proportion of MM; however they also had a compromised ability to grow. Mitochondrial functionality, in terms of coupling efficiency and spare respiratory capacity, was also impaired. Pro inflammatory cytokine profile was found in the supernatants of these cultures. This was associated with a reduced activity in the MSP related to mitochondrial fragmentation. Conclusion Cellular survival strategies, in the face of a chronic toxic stimulus, are a necessary requirement to ensure continuing functionality of the organ. We show here that growth retarded hepatocytes, which survived the EtOH insult, are characterised by a dramatic formation of MM, suggesting this as a mechanism to avoid death. We also show for the first time the involvement of MSP in this pathway, raising the potentiality for the use of these proteins as therapeutic targets and biomarkers in ALD. Disclosure of interest None Declared. ![Abstract PTH-094 Figure 1][1] Abstract PTH-094 Figure 1 Ethanol-induced megamitochondria (MM) formation visualised (a) by electron microscopy in human PCLS and (b) by confocal microscopy in VL-17A cells Reference 1. Altamirano, et al . Gastroenterology , 2014;146(5):1231–1239 [1]: pending:yes

P1116 : Are megamitochondria a cellular survival strategy for ethanol-induced liver toxicity?

P1116 : Are megamitochondria a cellular survival strategy for ethanol-induced liver toxicity?

Total phenolic, flavonoid contents, in-vitro antioxidant activities and hepatoprotective effect of aqueous leaf extract of Atalantia ceylanica.

BackgroundDecoction prepared from leaves of Atalantia ceylanica is used in traditional medicine in Sri Lanka for the treatment of various liver ailments since ancient times. Lyophilized powder of the water extract of A. ceylanica leaves was investigated for its phytochemical constituents, antioxidant and hepatoprotective activity in-vitro.MethodsThe total phenolic and flavonoid contents were determined using Folin Ciocalteu method and aluminium chloride colorimetric assay respectively. The antioxidant activities of the decoction were investigated using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical, nitric oxide scavenging assays and ferric ion reducing power assay. Hepatotoxicity was induced on porcine liver slices with ethanol to study hepatoprotective activity. Porcine liver slices were incubated at 37°C with different concentrations of the water extract of A. ceylanica in the presence of ethanol for 2 hours. The hepatoprotective effects were quantified by the leakage of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) to the medium. Thiobarbituric acid reactive substances (TBARS) assay was performed to examine the anti-lipid peroxidation activity caused by the plant extract.ResultsThe mean ± SD (n =9) for the levels of total phenolics and flavonoids were 4.87 ± 0.89 w/w% of gallic acid equivalents and 16.48 ± 0.63 w/w% of (-)-Epigallocatechin gallate equivalents respectively. The decoction demonstrated high antioxidant activity. The mean ± SD values of EC50 were 131.2 ± 36.1, 48.4 ± 12.1, 263.5 ± 28.3 and 87.70 ± 6.06 μg/ml for DPPH, hydroxyl radical, nitric oxide scavenging assays and ferric ion reducing power assay respectively.A significant decrease (p <0.05) was observed in ALT, AST and LDH release from porcine liver slices treated with A. ceylanica extract at a concentration of 2 mg/ml in the presence of ethanol (5 M) compared to that of ethanol (5 M) treated slices. Furthermore, a reduction in lipid peroxidation was also observed in liver slices treated with the leaf extract of A. ceylanica (2 mg/ml) compared to that of ethanol induced liver toxicity (p <0.05).ConclusionsThe results suggest that aqueous extract of A. ceylanica exerts hepatoprotective activity against ethanol induced liver toxicity of porcine liver slices which can be attributed to the antioxidant properties possessed by the plant material.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-395) contains supplementary material, which is available to authorized users.

Effects of vitamin C and E supplementation on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet

We compared the preventive capacity of high intakes of vitamin C (VC) and vitamin E (VE) on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet. Thirty-two Wistar rats received the low fat (10% of total calories) Lieber-DeCarli liquid diet as follows: either ethanol alone (Alc group, 36% of total calories) or ethanol in combination with VC (Alc + VC group, 40 mg VC/100 g body weight) or VE (Alc + VE group, 0.8 mg VE/100 g body weight). Control rats were pair-fed a liquid diet with the Alc group. Ethanol administration induced a modest increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), conjugated dienes (CD), and triglycerides but decreased total radical-trapping antioxidant potential (TRAP) in plasma. VE supplementation to alcohol-fed rats restored the plasma levels of AST, CD, and TRAP to control levels. However, VC supplementation did not significantly influence plasma ALT, AST, or CD. In addition, a significant increase in plasma aminothiols such as homocysteine and cysteine was observed in the Alc group, but cysteinylglycine and glutathione (GSH) did not change by ethanol feeding. Supplementing alcohol-fed rats with VC increased plasma GSH and hepatic S-adenosylmethionine, but plasma levels of aminothiols, except GSH, were not influenced by either VC or VE supplementation in ethanol-fed rats. These results indicate that a low-fat ethanol diet induces oxidative stress and consequent liver toxicity similar to a high-fat ethanol diet and that VE supplementation has a protective effect on ethanol-induced oxidative stress and liver toxicity.

Declinol, a Complex Containing Kudzu, Bitter Herbs (Gentian, Tangerine Peel)and Bupleurum, Significantly Reduced Alcohol Use Disorders Identification Test (AUDIT) Scores in Moderate to Heavy Drinkers: A Pilot Study

It is well established that inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However not all of the anti-alcohol properties of diadzin are due to inhibition of ALDH-2. This is in agreement with our earlier work showing significant interaction effects of both pyrozole (ALDH-2 inhibitor) and methyl-pyrozole (non-inhibitor) and ethanol's depressant effects. Moreover, it has been suggested that selective ALDH 2 inhibitors reduce craving for alcohol by increasing dopamine in the nucleus accumbens (NAc). In addition there is significant evidence related to the role of the genetics of bitter receptors (TAS2R) and its stimulation as an aversive mechanism against alcohol intake. The inclusion of bitters such as Gentian & Tangerine Peel in Declinol provides stimulation of gut TAS2R receptors which is potentially synergistic with the effects of Kudzu. Finally the addition of Radix Bupleuri in the Declinol formula may have some protective benefits not only in terms of ethanol induced liver toxicity but neurochemical actions involving endorphins, dopamine and epinephrine. With this information as a rationale, we report herein that this combination significantly reduced Alcohol Use Disorders Identification Test (AUDIT) scores administered to ten heavy drinkers (M=8, F=2; 43.2 ± 14.6 years) attending a recovery program. Specifically, from the pre-post comparison of the AUD scores, it was found that the score of every participant decreased after the intervention which ranged from 1 to 31. The decrease in the scores was found to be statistically significant with the p-value of 0.00298 (two-sided paired test; p-value = 0.00149 for one-sided test). Albeit this being a small pilot, we are encouraged about these significant results, and caution any interpretation until larger controlled studies are executed.

In Vivo prophylactic effects of oleanolic acid isolated from chloroform extract of Flaveria trinervia against ethanol induced liver toxicity in rats

The prophylactic effects of oleanolic acid (OA) isolated from chloroform extract (CE) of Flaveria trinervia against ethanol induced liver toxicity was investigated using rats. CE and OA at three different doses were tested by administering orally to the ethanol treated animals during the last week of the 7 weeks study. Silymarin was used as the standard reference. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin in ethanol treated animals were restored towards normalcy by treatment of CE and OA. In vivo antioxidant and in vitro free radical scavenging activities were also positive for all the three concentrations of CE and OA. However, OA at 150 mg/kg showed significant activity when compared to the other two doses. Biochemical observations in support with histopathological examinations revealed that CE and OA possess hepatoprotective action against ethanol induced hepatotoxicity in rats.

Hepatoprotective effects of purified oleuropein from olive leaf extract against ethanol-induced damages in the rat

Summary Olives and olive oil contain large amounts of oleuropein. This phenolic compound is responsible for their bitter taste and pungent aroma and has been recognized as a powerful hypotensive, hypoglycemic and antioxidant agent. Thus, the aim of the present study was to evaluate the antioxidant properties of oleuropein on ethanol-induced oxidative damage and to examine its beneficial effects on liver function. Thirty-two adult male Sprague-Dawley rats were divided into four equal groups: the first group served as untreated control. The second group of rats were given ethanol (4 g/kg) orally. Group 3 received oral oleuropein (15 mg/kg). The final group of rats were fed ethanol (4 g/kg), 120 min after oral administration of oleuropein (15 mg/kg). All of the treatments were applied for 4 weeks via gavage. Administration of ethanol to rats induced toxicity in their liver, as shown by the significant elevation in the serum levels of transaminases, total cholesterol as well as liver histopathological findings. Elevation of glutathione peroxidase activity, the hepatic main antioxidant enzyme, and total glutathione was observed to suppress oxidative stress in the ethanol group. TBARS (an indicator of lipid peroxidation) concentration is also increased in ethanol-treated rats. In contrast, oleuropein during ethanol treatment in rats resulted in a higher antiperoxidative enzyme activity, catalase, and inhibited toxicity to the liver, as monitored by the reduction in ALT and AST levels and TBARS concentration. It is suggested that oleuropein possesses beneficial antioxidant effects against ethanol-induced liver toxicity, and therefore use of olive leaf extract may have prophylactic value in reducing the common complications resulting from oxidative stress in alcoholism.

Alcohol metabolizing and antioxidant activities of complex herbal extracts from medicinal plants

The objective of this study was to evaluate the alcohol-metabolizing and antioxidative activities of complex herbal extract (CHE). The alcohol-metabolizing activity of CHE was evaluated by assessing alcohol dehydrogenase (ADH) activity, acetaldehyde dehydrogenase (ALDH) activity, and protective effect against alcohol induced damage in in vitro and in vivo models. In this study, CHE treatment significantly increased ADH and ALDH activities and reduced cell death in alcohol-induced liver cell damage. Moreover, it also significantly reduced the serum alcohol and acetaldehyde concentrations in alcoholfed rats. To define the effect of CHE on alcohol metabolism, its antioxidative activities were estimated by measuring radical scavenging activity, ferric-reducing antioxidant potential ability, and thiobarbituric acid reactive substance, and the results demonstrated a higher antioxidative capacity of CHE than the vitamin C control at a high dose (10 mg/mL). Therefore, this study suggests that CHE can be a potential natural resource for the management of ethanol-induced liver toxicity.