Effects of a combination of Japanese Raisin Tree Seed and Flower of Lobed Kudzuvine against acute alcohol-induced liver injury in mice

Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.

The triterpenoids-enriched extracts from Antrodia cinnamomea mycelia attenuate alcohol-induced chronic liver injury via suppression lipid accumulation in C57BL/6 mice

The major pathologic hallmark of the alcoholic liver disease(ALD)is the representation of chronic alcohol-induced hepatocyte lipid accumulation.This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia(ACT)in chronic alcohol-induced liver injury mice,establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks.In longterm alcohol consumption mice,the significantly lost body weight,increased organ indexes,hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration,showing its hepatoprotective property.ACT suppressed the triglyceride,total cholesterol and low-density lipoprotein levels,and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice.Combining with the pathological observations,ACT displayed an anti-steatosis effects to restrain the progress of ALD.Based on proteomic analysis and enzyme-linked immunosorbent assay,ACT had been confi rmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species.According to further data,ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1αand NF-κB signaling.In summary,ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.

Alcohol-Induced Cardiomyopathy Presenting with Left Ventricular Apical Thrombus

Background: Chronic excessive alcohol consumption has been strongly associated with alcohol-induced cardiomyopathy (AC) in patients with no evidence of coronary artery disease (CAD). AC may cause cardiovascular complications and significant impact on the quality of life. We discuss an interesting case of dilated cardiomyopathy, associated complication, diagnostic work-up and management. Case Report: A young male presented to our service with worsening dyspnea, orthopnea, and scrotal and lower extremity edema. On average, he consumed a pack of 12 beers every day and had a 30-pack-years smoking history. He was found to be in acute heart failure with evidence of pulmonary edema and cardiomegaly on chest imaging. He had biventricular dilatation and severely reduced left ventricular ejection fraction (LVEF) 15% in addition to a thrombus in the LV apex. The cardiac catheterization was unremarkable for CAD. He was diuresed appropriately resulting in significant weight loss and resolution of symptoms. LV thrombus was treated with unfractionated heparin infusion that was transitioned to warfarin. He was maintained on guidelines-directed medical therapy for heart failure. Extensive counseling was provided regarding alcohol and tobacco cessation. On follow-up echocardiogram, his LVEF improved and there was no evidence of LV thrombus. We think, the readership will benefit from our experience of treating a case of AC, and the importance of clinical history. Conclusion: Chronic excessive alcohol use is detrimental to cardiac function leading to alcohol-induced cardiomyopathy. A careful approach to clinical history of alcohol consumption and prompt diagnostic workup negative for ischemic causes may confirm the diagnosis. Cardiac function improves with guidelines-directed medical therapy for heart failure and abstinence from alcohol.

Protection role of resveratrol against alcohol-induced heart defect in zebrafish embryos

To the Editor:Alcohol-induced heart defect is one of the most important clinical manifestations of fetal alcohol spectrum disorder(FASD),characterized by atrioventricular septal defect and arterial conical deformity.[1]Resveratrol,a polyphenol component of the traditional Chinese herb Polygonum cuspidatum,which is mainly extracted from its rhizome,is known to exhibit beneficial effects on the cardiovascular system.For example,resveratrol has beneficial effects on heart dysfunction,myocardial hypertrophy,and pressure overload.Moreover,resveratrol was found to inhibit platelet aggregation,prevent atherosclerosis,and scavenge free radicals.[2]However,the effect of resveratrol on alcohol-induced heart defect during heart formation is still unknown.The unique characteristics of zebrafish embryos,such as their transparent body,in vitro fertilization,and short reproductive cycle,make them an attractive tool for cardiovascular research.Moreover,the immersion-based alcohol delivery method used with zebrafish embryos is non-invasive unlike most of the alcohol administration protocols applied in rodent models.

Lysosome and proteasome dysfunction in alcohol-induced liver injury

The review describes research findings on the influence of alcohol consumption on two crucial catabolic systems in hepatocytes:the lysosome and the ubiquitin-proteasome system(UPS).The lysosome is a membrane-bound organelle that degrades all aging and/or damaged organelles and hydrolyzes all forms of macromolecules.The UPS is mostly proteolytic.It carries out the majority of its functions in the soluble portion of the cytoplasm(cytosol)and degrades nearly all intracellular proteins,particularly those with short half-lives,so that their levels are tightly controlled.Our review will briefly discuss the epidemiology of alcohol abuse and the spectrum of alcohol-induced liver disease(AILD).We will explain why ethanol(EtOH)metabolism,but not EtOH alone,is hepatotoxic.Then,we will summarize how heavy drinking alters hepatic catabolic systems,resulting in liver enlargement that develops from hepatocyte swelling due,in part,to aberrant accumulation of undegraded lipid droplets(steatosis)and undegraded proteins(proteopathy).Our detailed description of each catabolic system will highlight its discoverer(s)and emphasize each system’s characteristics.Most important,we will review the evidence that chronic EtOH consumption disrupts hepatic lysosome biogenesis and inhibits the UPS by impeding hepatic proteasome activity.It will become evident that each of these EtOH-induced defects has far-reaching functional consequences.Finally,we will describe current and potential therapeutic interventions for alleviating EtOH-induced liver injury.The most effective intervention is the cessation of EtOH consumption.However,there are other potential approaches using natural or synthetic compounds that activate autophagy or the proteasome to enhance the degradation of accumulated lipid droplets or proteins,respectively,which could alleviate AILD.These approaches,now in their early stages of investigation,will also be discussed in this review.

Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease

AIM To evaluate risk of recidivism on a case-by-case basis.METHODS From our center's liver transplant program,we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium(OSOTC) exception criteria.They were considered to have either a low or medium risk of recidivism,and had at least one or three or more months of abstinence,respectively.They were matched based on gender,age,and Model for End-Stage Liver Disease(MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data.RESULTS Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls.Nineteen patients(53%) with a median [Inter-quartile range(IQR)] MELD score of 24(13) received transplant and were followed for a median of 3.4 years.They were matched to 38 controls with a median(IQR) MELD score of 25(9).At one and five years,cumulative survival rates(± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls,respectively(Log-rank test,P = 0.837).Four(21%) patients resumed drinking by last follow-up visit.CONCLUSION Compared to traditional criteria for assessment of risk of recidivism,a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation.