Acute Alcohol-induced Liver Injury Research Articles

Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

Geniposide protects against acute alcohol-induced liver injury in mice via up-regulating the expression of the main antioxidant enzymes.

Geniposide (GP) is one of main compounds in Gardenia jasminoides Ellis, with both medicinal and nutritional value. This study was designed to determine, for the first time, how GP from G. jasminoides protects against acute alcohol-induced liver injury, and the underlying mechanisms. Mice were orally administered alcohol (6.0 g/kg body mass) 2 h after intragastric administration of GP and bifendate, every day for 7 continuous days. Six hours after the alcohol was administered, levels of serum alanine/aspartate transaminase (ALT/AST), hepatic lipid peroxidation (LPO), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), copper- and zinc-containing superoxide dismutase (CuZn-SOD), and catalase (CAT), and mRNA expression of CuZn-SOD and CAT were assayed. The results demonstrated that GP (20.0, 40.0, or 80 mg/kg) significantly reversed the excessive, alcohol-induced elevation in both serum ALT/AST and hepatic LPO levels. Moreover, hepatic GSH, GST, GPx, CuZn-SOD, and CAT levels were all decreased in the alcohol-treated mice, whereas treatment with GP reversed these decreases. Further analysis indicated that hepatic mRNA expression of CuZn-SOD and CAT in the alcohol-treated mice was significantly down-regulated, whereas GP up-regulated such decreases. Taken together, this study shows that GP protects against acute alcohol-induced liver injury via up-regulating the expression of the main antioxidant enzymes, and thus ameliorates alcohol-induced oxidative stress injury in the liver.

The hepatoprotective effect of aqueous extracts of Penthorum chinense Pursh against acute alcohol-induced liver injury is associated with ameliorating hepatic steatosis and reducing oxidative stress.

The aim of the present study was to evaluate the effects of Penthorum chinense Pursh (PCP), a health food and folk medicine, against acute alcohol-induced liver injury and further to elucidate its probable mechanisms. Male C57BL/6 mice were treated with an aqueous extract of PCP (5.2 and 10.3 g per kg BW) once daily for 7 consecutive days prior to ethanol gavage (4.7 g kg(-1)) every 12 h for a total of three doses. Pretreatment with PCP significantly decreased the elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic triglyceride after the last ethanol administration. PCP suppressed the elevation of the malondialdehyde (MDA) level, restored the glutathione (GSH) level and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in both the serum and liver, which were associated with the inhibition of hepatic cytochrome P450 2E1 (CYP2E1). In addition, alcohol exposure markedly induced the lipolysis of white adipose tissue (WAT) through up-regulating protein expressions of adipose triglyceride lipase (ATGL) and phosphorylation of hormone-sensitive lipase (p-HSL), and enhancing the fatty acid uptake capacity in the liver by elevated hepatic CD36 expression, which were attenuated by PCP treatment. These data demonstrated that pre-treatment with PCP protected against acute ethanol-induced liver injury, possibly by reducing CYP2E1-dependent oxidative stress and ameliorating dysfunctional WAT derived-fatty acid influx to the liver. Our findings suggest that PCP might be a promising agent for the prevention of acute alcohol-induced liver injury.

Impact of age on acute alcohol induced liver injury and hepatocyte apoptosis

Impact of age on acute alcohol induced liver injury and hepatocyte apoptosis

Preparation of total flavonoids from loquat flower and its protective effect on acute alcohol-induced liver injury in mice

This study aimed to research the preparation techniques of total flavones from loquat flower (TFLF), its anti-oxidation capacity, and its protective effect on hepatic injury. The best extraction parameters by orthogonal experimentation were water at 100°C, extraction time 2.5 hours, solid/liquid ratio 1:20, and three decoctions. The chromogenic reaction to the flavones showed that loquat flowers mainly contained flavone, flavonol, and flavanone compounds combining ortho-phenolic hydroxyl group structure in the 10–30% ethanol fraction. The anti-oxidant capacity of O2−· was 26.09% and of OH−·was 83.01% by salicylic acid and pyrogallol auto-oxidation. Compared with the model group, TFLF lowered the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, and malondialdehyde and liver index significantly, and upregulated the expression of adipose triglyceride lipase and Heine oxygenase-1 mRNA. The present findings suggest that TFLF has protective effect on acute alcoholinduced liver injury in mice and may be related to its antioxidant and free-radical scavenging activity.

Protective effects of maslinic acid against alcohol-induced acute liver injury in mice

Protective effects of maslinic acid (MA) at 10, 15 or 20 mg/kg body weight/day against alcohol-induced acute hepatotoxicity in mice were examined. Mice were administrated by MA for 3 weeks, and followed by alcohol treatment. Results showed that MA pre-intake at three doses resulted in its accumulation in the liver; and dose-dependently lowered cytochrome P450 2E1 activity and protein expression at 23.5–51.2% and 21.4–62.3%, respectively (P < 0.05). MA pre-intake decreased subsequent alcohol-induced reactive oxygen species, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, nitric oxide and prostaglandin E2 production; retained glutathione content; maintained catalase and glutathione peroxidase activities; and declined cyclooxygenase-2 and total nitric oxide synthase activities in the liver (P < 0.05). Furthermore, MA pre-intake suppressed 17.3–51.7% nuclear factor kappa (NF-κ)B p50, 23.5–58.8% NF-κB p65, 25.6–62.4% p-p38 and 24.1–63.0% p-JNK expression in the liver (P < 0.05). Histological data indicated that MA intake at test doses attenuated hepatic inflammatory infiltrate. These findings support that maslinic acid is a potent preventive agent against acute alcoholic liver disease.

후코이단이 쥐의 급성 알콜성 간손상에 미치는 영향

본 연구는 해조류에 존재하는 황산기를 함유하고 있는 후코이단의 급성 알코올 간 손상 모델에서의 간 보호능을 관찰하였다. 실험 결과 후코이단은 급성으로 알코올을 섭취시킨 쥐의 체중감소를 억제시켰으며, 알코올 섭취를 통해 나타날 수 있는 중성지질, 콜레스테롤, LDL-콜레스테롤 상승을 유의적으로 감소시킨 것으로 나타났다. 또한 간 기능을 대표하는 혈중의 GOT는 유의적인 차이는 없었으나, GPT는 유의적으로 후코이단 경구투여에 의해 감소되었다. 또한 후코이단은 지방이 비대해 지는 현상과 간세포의 지방축척을 감소시킨 것으로 관찰되었다. 따라서 이러한 결과로 보아 후코이단은 급성 알코올 섭취에 의한 간손상을 완화시켜 줄 수 있는 식품소재로 활용가능하다고 사료된다. The purpose of this study was to investigate the protective effects of fucoidan on acute alcohol-induced liver injury in rats. Experimental animals were randomly divided into four groups: (1) a control group, (2) a group fed 25% ethanol, (3) a group fed 25% ethanol and 250 mg/kg BW of fucoidan (25% ethanol+FUCO250), and (4) a group fed 25% ethanol and 500 mg/kg BW of fucoidan (25% ethanol+FUCO500). Each group was fed orally two times per day for 15 days. Liver weights in the 25% ethanol group were increased compared to the control group, while liver weights in the 25% ethanol+FUCO500 group were significantly decreased compared to the 25% ethanol group (p<0.05). Plasma concentrations of triglyceride, cholesterol, and LDL-cholesterol were elevated in the 25% ethanol group; however, these levels in the 25% ethanol+FUCO250 group were significantly decreased compared to the 25% ethanol group (p<0.05). The glutamic-pyruvic transaminase activity of the 25% ethanol+FUCO500 group also was significantly lower than the 25% ethanol group (p<0.05). These results indicate that fucoidan might protect against acute alcohol-induced liver injury.

Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice

The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-α in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care.

알코올 및 사염화탄소에 의해 유발된 급만성 간손상에 대한 지구자 열수추출물의 보호효과

Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and <TEX>$CCl_4$</TEX> in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute <TEX>$CCl_4$</TEX>-induced liver injury, rats received a single dose of <TEX>$CCl_4$</TEX> (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after <TEX>$CCl_4$</TEX> administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and <TEX>${\gamma}$</TEX>-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and <TEX>${\gamma}$</TEX>-GTP levels compared to control group. In acute <TEX>$CCl_4$</TEX>-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute <TEX>$CCl_4$</TEX>-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.

Intestinal Alkaline Phosphatase Prevents Acute Alcohol-Induced Liver Injury

Intestinal Alkaline Phosphatase Prevents Acute Alcohol-Induced Liver Injury

Hepatoprotective Effects of Triterpenoid Isolated from Schizandra chinensis against Acute Alcohol-Induced Liver Injury in Mice

Hepatoprotective Effects of Triterpenoid Isolated from Schizandra chinensis against Acute Alcohol-Induced Liver Injury in Mice

Preliminary characterization, antioxidant activity in vitro and hepatoprotective effect on acute alcohol-induced liver injury in mice of polysaccharides from the peduncles of Hovenia dulcis

The fresh fleshy peduncles of Hovenia dulcis have been used as a food supplement and traditional herbal medicine for the treatment of liver diseases and alcoholic poisoning for more than a millennium. The objectives of the present study, therefore, were to determine the antioxidant activity of polysaccharides from the peduncles of H. dulcis (HDPS) and to evaluate its hepatoprotective effect on acute alcohol-induced liver injury in mice. HDPS, prepared by hot water extraction, ethanol precipitation and treatment of macroporous resin, was found to be non-starch polysaccharide and mainly composed of galactose, arabinose, rhamnose and galacturonic acid. In in vitro antioxidant assay, HDPS exhibited high superoxide radical scavenging activity, strong inhibition effect on lipid peroxidation and a medium ferrous ion-chelating activity. For hepatoprotective activity in vivo, the administration of HDPS significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, significantly decreased the liver level of malondialdehyde and remarkably restored the liver activities of superoxide dismutase and glutathione peroxidase in alcohol-induced liver injury mice. The results suggested that HDPS had a significant protective effect against acute alcohol-induced liver injury possibly via its antioxidant activity to protect biological systems against the oxidative stress.

PTU-009 Alcohol-induced liver toxicity is associated with neutrophil dysfunction in a novel in-vitro model of acute liver injury

IntroductionSepsis is a major cause of mortality in patients with alcohol-induced acute and chronic liver failure (ALF/CLF). Neutrophils are a major innate immune cell subset involved in the first line...

Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury

Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (10(9) colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury.

Discrepant roles of CpG ODN on acute alcohol-induced liver injury in mice

Increasing evidence suggests that the alcoholic liver injury is associated with activation of Toll-like receptors (TLRs) and the consequent over-production of inflammatory cytokines such as TNF-α. However, few studies have evaluated the effect of CpG ODN, a TLR9 agonist, on alcoholic liver injury. In this study, an animal model of acute alcohol-induced liver injury was established by administering the mice with alcohol at 7g/kg intragastrically once. Using the model, 2216, an A-type CpG ODN, was found able to dramatically elevate serum ALT levels and aggravate pathological changes of liver in mice. In contrast, 2006, a B-type CpG ODN, caused elevation of serum ALT levels with no visible aggravation of liver pathological changes; YW002, a C-type CpG ODN, caused no elevation of serum ALT levels and seemed able to lessen pathological changes in the liver of the mice. Real-time RT-PCR revealed that 2216 dramatically up-regulated the expression of TLR9 and TNF-α and YW002 was unable to up-regulate expression of TLR9 and TNF-α, instead up-regulate the expression of IFN-α in the livers of the model mice. The data suggest that 2216 could aggravate alcohol-induced liver injury by inducing the up-regulation of hepatic TLR9 and TNF-α and that YW002 could alleviate the pathological changes induced by acute alcohol intake by up-regulating IFN-α, possibly.

Protective effect of Lysimachia christinae against acute alcohol-induced liver injury in mice

Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study was undertaken to investigate protection of L. christinae against acute alcohol-induced liver injury in mice, the related mechanism of oxidative stress and its hepatoprotective chemical compound for the first time. Mice were orally administered alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L. christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric administration (i.g.) except the normal group. Serum and liver tissue samples were collected 6 h after alcohol administration and the amount of quercetin in ET was analyzed by high-performance liquid chromatography (HPLC) with a diode array detector (DAD). The results showed that alcohol-induced elevated serum alanine transferase (ALT) and aspartate transaminase (AST) activities were significantly reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg), respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels significantly decreased, while glutathione amounts, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities all increased in livers of ET-, quercetin-, and bifendate-treated mice. Besides, amount of quercetin in ET was 1.03%. Taken together, our results indicate that L. christinae can protect against acute alcohol-induced liver injury in mice, the potential mechanism can be related to inhibiting liver oxidative stress injury, and its main hepatoprotective compound is quercetin, for the first time.

Acute Alcohol-Induced Liver Injury

Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD) in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation, and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, which also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

Development of a mouse model of alcohol-induced acute liver injury

Development of a mouse model of alcohol-induced acute liver injury

Interleukin-22 Protects against Acute Alcohol-Induced Hepatotoxicity in Mice

The protective effects of interleukin-22 (IL-22) on acute alcohol-induced liver injury were investigated. Mice were gavaged with 7 doses of alcohol (56% wt/vol, 15.2 mL/kg of body weight for each dose) over the 24 h, and IL-22 (0.5 mg/kg BW) was given to the mice by injection into the tail vein 1 h after alcohol administration. The results indicated that acute alcohol administration caused prominent hepatic microvesicular steatosis and an elevation of serum transaminase activities, induced a significant decrease in hepatic glutathione in conjunction with enhanced lipid peroxidation, and increased hepatocyte apoptosis as well as hepatic TNF-alpha production. IL-22 treatment attenuated these adverse changes induced by acute alcohol administration. The protective effects of IL-22 on alcohol-induced hepatotoxicity were due mainly to its anti-inflammatory, anti-oxidant, and anti-apoptotic features.

Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice

Matrix metalloproteinases (MMPs) have been implicated in inflammatory and degradative processes in several diseases. The study aims to explore the mechanism of MMP-9 regulation in alcohol-induced acute liver injury and its protection by melatonin in mice. Alcohol-induced acute liver injury was induced in female Balb/C mice by ethanol administration and protection studies were carried out with a well-known antioxidant molecule, melatonin. Degree of liver injury was monitored by histological and biochemical analysis of liver tissues. Oral administration of ethanol in mouse caused significant increase in alanine amino transferase (ALT) activity in serum. Depletion of glutathione and enhancement of lipid peroxidation as well as protein oxidation was observed in liver tissues following ethanol treatment. However, melatonin exhibited potent hepatoprotective activity by inhibiting ALT activity and oxidative stress. Additionally, MMP-9 expression was increased by ethanol in a dose and time dependent manner in liver tissue and serum. Increased secretion of proMMP-9 was strongly correlated with the expression of proinflammatory cytokines e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL6. Melatonin showed hepatoprotective role by downregulation of MMP-9 and upregulation of tissue inhibitor of metalloproteases (TIMP-1) expression in liver tissue. Nuclear factor (NF)-κB, plays an important role in inducing inflammatory genes during oxidative stress, thus the role of NF-κB in ethanol-induced liver injury was investigated. Ethanol induced nuclear translocation of NF-κB and increased degradation of inhibitor of NF-κB (IκBα) in liver tissues. Moreover, ethanol-induced NF-κB translocation into nucleus was inhibited significantly by melatonin. This is the first study to elucidate the induction of MMP-9 expression by NF-κB-dependent pathway in ethanol-induced acute liver injury in mice. This study also identifies the novel role of melatonin in hepatoprotection via MMP-9 down regulation.