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As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.
Subject(s)
Animals , Mice , Chemical and Drug Induced Liver Injury , Ethanol , Liver/metabolism , Liver Diseases, Alcoholic , Oxidative Stress , StomachABSTRACT
Objective:To study the protective effect of Ficus pandurata extract on acute alcoholic liver injury based on pyroptosis mechanism.Method:The 56 male C57BL/6 mice were randomly divided into normal control group， model control group， positive control group（60 mg·kg-1）， fresh medicine water extract group（48 g·kg-1）， dry drug water extract group（48 g·kg-1），dry drug 50% alcohol extract group（48 g·kg-1） and dry drug 95% alcohol extract group （48 g·kg-1）， 8 mice in each group.Positive control and different solvent extract groups of Ficus tenuifolia were intragastrically administrated for 18 days，once a day，while normal group and model group were given the same volume of pure water intragastrically. After 15 days of continuous gavage， mice received 50％ ethanol（12 mL·kg-1）intragastrically for 3 days to induce acute alcoholic liver injury model except for the normal control group. At 14 h after the last treatment，serum and liver samples were obtained，the serum content of alanine aminotransferase （ALT） and aspartate transaminase（AST） were determined， the histopathologic changes of the hepatic tissues were observed by hematoxylin ecosin（HE） staining.The content of malondialdehyde (MDA) in liver was determined by thiobarbituric acid (TBA) and the content of lactate dehydrogenase (LDH) was determined by microplate method. Western blot and TUNEL assay kit was used to detect the cell pyroptosis rate.Result:Compared with normal group， ALT， AST， MDA and LDH levels in the model group were significantly increased， liver index was significantly increased，TUNEL staining positive， inflammatory factors and pyroptosis related protein expressions were significantly increased （P<0.05）. Compared with model control group， the ALT，AST ，MDA and LDH of the drug intervention group decreased significantly （P<0.05）. The liver index decreased in different degrees， and the expression of inflammatory factors and pyroptosis related protein in the water extract treatment group decreased significantly （P<0.05）.Conclusion:The root extract of Ficus pandurata Hance has protective effect on acute alcoholic liver injury， and the mechanism of water extract might relate to inhibiting hepatocyte pyroptosis.
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Aim To investigate the protective effect of immunomodulating peptide(PGPIPN) on the acute al-coholic liver injury in mice. Methods Kunming mice were randomly divided into control group, model group,glutataione(GSH) group, PGPIPN low dose group, PGPIPN moderate and high dose groups. The mice were treated with different doses of PGPIPN or GSH for two weeks except control group and model group. The acute alcoholic liver injury model was in-duced by gavage with 56° alcohol for three days. The indices including the activities of AST,ALT in serum, and the contents of TNF-α, MDA, SOD and GSH-Px in liver were examined. Liver histopathological changes were examined by HE staining. Results Compared with control group,the levels of serum ALT,AST and the contents of TNF-α, MDA significantly increased, while the contents of SOD and GSH-Px significantly de-creased in model group. There was hepatocyte apopto-sis and inflammatory cell infiltration in liver tissues. Compared with model group, the activities of serum ALT, AST and the contents of TNF-α, MDA were re-markably reduced in PGPIPN high dose group. The contents of SOD and GSH-Px significantly increased in PGPIPN high dose group. PGPIPN could alleviate the injury of liver. Conclusion PGPIPN has certain pro-tective effect on acute alcoholic liver injury of mice, providing a theoretical guidance.
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Objective To study the effect of Pinus yunnanensis on acute alcoholic liver injury in rats and explore its mechanism. Methods A model of acute alcoholic liver injury in mice was prepared by alcohol. The mice were randomly divided into normal control group, model group, positive control group, Pinus yunnanensis low-, medium-and high-dose groups. Mice in the medicine group were given the corresponding medicine by gavage once a day for 7 days. After the last three hours of intragastric administration, the liver and spleen index, ALT, AST and GSH in serum, SOD, MDA and NO in liver homogenates were measured. Histopathological changes of liver were observed by HE staining. Results Compared with model group, Pinecone of Pinus unnanensis high-, medium- and low-dose groups could significantly reduce the liver index in mice (P0.05). HE staining results showed that, the damage of liver tissue in mice of Pinus yunnanensis was significantly improved compared with the model group. Conclusion Pinus yunnanensis has protective effects on acute alcoholic liver injury in mice.
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This study aimed to explore the value of animal energy metabolism monitoring system (AEMMS) to evaluate the energy metabolism of acute alcohol liver injury in rat with the treatment of acupuncture.Tirty rats were randomly divided into the control group,the model group and the EA group.The model group and the EA group were gavaged with 50％ ethanol for the establishment of the animal model of acute alcoholic liver injury.EA was given by needling Zusanli (ST-36) 30 min after intragastic administration every day in the EA group.The treatment of acupuncture continued 3 days.In addition,the RER,heat,feeding and drinking were continuously recorded for 96 h in each group at the same time by AEMMS.As a result,the RER,feeding and drinking indices significantly decreased in rats with ALI with an increase in the heat index.There was an up-going tendency of the RER,feeding and drinking indices,and a declined tendency of the heat index in the model rats after EA treatment.It was concluded that AEMMS presented a practical value in the study of the energy metabolism of rats with ALI with the treatment of acupuncture.
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Objective To study the proliferation and apoptosis of related proteins in pathological liver tissues of alcohol-induced mice,and establish a model and time-evolution rule of liver cell apoptosis,which can be used to guide the clinical treatment of acute alcoholic liver injury.Methods A total of 30 male KM mice were fed in a clean grade animal room at the Capital Medical University and then randomly (random number) separated into two groups.The 10 mice in the normal group were fed without ethanol,while the other 20 mice in the experimental group were given a one-time grant of 50％ ethanol (12 mL/kg) by gavage.The mice in the experimental group were killed at two time points,6 h for 10 mice and 12 h for the other 10,after the intragastric administration.Hematoxylin and eosin (HE) staining was used to observe the morphological changes of liver in mice.The concentrations of T-ERK,p-ERK,PKC,p-PKC and caspase-3 were determined by the Western-blot method.The data were analyzed by Analysis of variance (ANOVA) method using statistical software SPSS 11.5 and criterion P ＜ 0.05 is chosen to determine differences that are statistically significant.Results By observing the behavioral changes and morphological indexes of mice,we confirmed the success of the model for acute alcoholic liver injury.During the process of re-building the model,no mice died.The mice in the experimental group appeared in drunken states,such as sleepiness and slowness of movement.Compared to the normal group,the experimental subgroup at the 6 h point showed no difference statistical significant; while the experimental subgroup at the 12 h point showed obvious histological changes in tissues,including the disorder of hepatic lobule structure and fatty vacuolization of hepatocytes.At the same time,in the experimental subgroup at the 12 h point,both P-ERK and P-PKC significantly decreased [(2.41 ±0.38),(0.97 ±0.25),F=4.82,P＜0.05; (0.16 ±0.00),(0.08 ± 0.01),F =29.63,P ＜ 0.05],but caspase-3 significantly increased [(0.30 ± 0.02),(0.11 ± 0.01),F =34.38,P ＜ 0.05].Conclusions In mice after intragastric administration of large doses of alcohol,the hepatic cell apoptosis appeared mainly after 6 h but before 12 h,therefore 6 ～ 12 h might be the time window to inhibit the cell apoptosis of mice' s acute liver injury from alcohol induction.