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Objective To investigate the dynamic changes in intestinal alpha-defensin-5 (RD-5),beta-defensin-2 (BD-2) mRNA after acute liver failure(ALF),and to explore their role in ALF.Methods A total of 60 C57BL5 mice were divided into 4 groups by means of random number table method:normal control group,ALF group,E.coli via gavage group and ALF + E.coli via gavage group.Intraperitoneal injection of D-galactosamine (500 mg/kg) and lipopolysaccharide(10 μg/kg) to make the model,in addition,ALF mice were fed with E.coli,and the observation time was 6 hours,12 hours,and 24 hours after modeling,and each time point had 6 specimens.Real-time PCR was used to test the RD-5 mRNA and BD-2 mRNA levels in the ileum tissue.Results The levels of RD-5 and BD-2 showed dynamic change in the experiment of ALF.Compared with the levels of RD-5 and BD-2(11.25 ±0.74,23.86 ±0.39) of the normal control group,the levels of RD-5 and BD-2 in ALF group and E.coli via gavage group increased at 6 hours after modeling(14.19 ±0.39,26.79 ± 0.36 and 12.57 ± 0.68,26.45 ± 0.85),and the differences were significant(all P＜0.05);at 12 hours after modeling,the RD-5 and BD-2 reached to the maximum concentration(15.76 ±0.33,29.10 ± 0.61 and 12.90 ± 0.96,27.42 ± 0.71),and the differences were statistically signi-ficant (all P ＜ 0.05).The degree of elevation of BD-2 was higher than RD-5.Later,they gradually declined.Conclusions RD-5 and BD-2 may play an important role in the pathogenesis of intestinal endotoxemia in experimental ALF.
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ObjectiveTo investigate the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on acute liver failure (ALF) induced by D-galactosamine (D-GalN) in rats. MethodsA total of 105 male Sprague-Dawley rats were randomly divided into healthy control group, liver failure model group, and rhG-CSF group, with 35 rats in each group. A rat model of ALF was established by intraperitoneal injection of D-GalN (1400 mg/kg). Alanine aminotransferase (ALT) level in the liver, total bilirubin (TBil), peripheral blood leukocyte count, and liver pathological changes were observed at 12, 24, 48, 72, and 120 hours after modeling, and survival rate was observed at 120 hours after modeling. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the LST-t test was used for further comparison between two groups. ResultsCompared with the liver failure model group, the rhG-CSF group had a significantly higher degree of hepatocyte degeneration and necrosis at all time points except 120 hours after modeling, and compared with the liver failure model group at 120 hours after modeling, the rhG-CSF group had better recovery of lobular structure on HE staining. Compared with the liver failure model group, the rhG-CSF group had a tendency of increase in the percentage of cells with positive tumor necrosis factor-α at the five time points after modeling. Compared with the liver failure model group, the rhG-CSF group had significantly higher levels of ALT and TBil at all five time points. Both groups had a significant change in ALT level at 24 hours after modeling (P＜0.05), as well as a significant change in TBil at 24, 48, and 120 hours after modeling (P＜0.05). The rhG-CSF group had a significantly higher peripheral blood leukocyte count than the liver failure model group at all five time points (all P＜005). There was no significant difference in survival rate at 120 hours after modeling between the two groups (P＞0.05). ConclusionApplication of rhG-CSF during the stage of acute inflammatory reaction of ALF may aggravate liver inflammatory response.
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Background@#Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored.@*Methods@#BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups.@*Results@#AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced.@*Conclusions@#These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.
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Objective To study the protective effect and mechanism of maslinic acid (MA) on acute liver injury (ALI) in rats.Methods Fifty BALB/c mice were randomly divided into control group,model group,and low (12.5 mg/kg),medium (25.0 mg/kg) and high doses (50.0 mg/kg) of MA,with 10 rats in each group.The control group was intraperitoneally injected with normal saline.The other groups were intraperitoneally injected with lipopolysaccharide (LPS) (50 mg/kg) and D-Gal N (500 mg/kg) to prepare mouse AL[model.The MA groups were administered with 12.5,25.0,50.0 mg/kg MA 1 h before model establishment,respectively.All the mice were sacrificed 6 h after model establishment,and serum and liver tissues were collected.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured.Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue.Thiobarbituric acid method was used to determine malondialdehyde (MDA).H2O2 reaction product colorimetric was used to determine the content of myeloperoxidase (MPO).The tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue was detected by enzyme-linked immunosorbent assay,respectively.Western Blot was conducted to detect the expression of nuclear factor E2 related factor 2 (Nrf2),heme oxygenase-1 (HO-1) and the activation of nuclear factor-kappa B (NF-κB) pathway.Results Compared with the model group,the liver histopathology in the low,medium and high doses MA groups was significantly improved.The serum ALT and AST levels were decreased,and the differences were statistically significant (all P＜0.05).The contents of MDA and MPO in liver tissues were decreased,and the differences were statistically significant (all P＜0.05).The protein contents of Nrf2 and HO-1 were increased,the differences were statistically significant (all P＜0.05).The NF-κB pathway was inhibited,and the differences were statistically significant (all P＜0.05).The levels of TNF-α and IL-6 in serum and liver tissues were decreased,and the differences were statistically significant (all P＜0.05).Conclusions MA has a protective effect on LPS/D-Gal N-induced ALI,and its mechanism is related to inhibition of NF-κB pathway and activation of Nrf2/HO-1 pathway.
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Objective To investigate the anti-injury and anti-inflammation protective effects of metformin in acute-liver-injury SD rat model induced by D-galactosamine and Pam3CSK4 .Methods Eighteen male Sprague-Dawley rats were treated with the mixture of D-galactosamine (350 mg/kg ) and Pam3CSK4 (50 μg/kg ) by intraperitoneal injection (i .p .) to construct acute liver injury model .The rats in intervention group were given PBS and metformin ,respectively .The liver and body weight were measured and the ratio of liver weight to body weight was calculated .HE staining was used to observe the pathological changes of the liver .Fasting serum was collected for detection of serological parameters .ELISA and RT-qPCR were used to determine the expression levels of IL-6 and TNF-α.Finally , activation of MAPK signal pathway in rat liver was detected by Western blot .Results Compared with those in control group , the ratio of body weight to liver weight , serum transaminase and proinflammatory cytokines IL-6 and TNF-a were all significantly increased in the two intervention groups .Meanwhile , hepatic degeneration and hepatic interstitial exudation indicated that D -galactosamine combined with Pam3CSK4 successfully constructed acute liver injury model in the SD rats.Compared with PBS group, the ratio of body weight to liver weight , hepatic damage , serum transaminase levels.and the expressions of proinflammatory cytokines IL-6 and TNF-a were significantly decreased in metformin-treated group.Meanwhile,the expressions of p-ERKl/2,p-SAPK/JNK and p-P38 MAPK decreased in liver tissues by metformin pretreatment,suggesting that metformin may play an anti-inflammatory effect by suppressing MAPK signaling pathway.Conclusion Metformin attenuated inflammatory reactions in SD rats with acute liver injury induced by D -galactosamine and Pam3CSK4.
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Objective@#To investigate the role of the glycogen synthase kinase 3β (GSK3β) and the peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway in acute liver failure and related mechanisms in a mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS).@*Methods@#C57BL/6 mice were given intraperitoneal injection of D-GalN/LPS to establish a mouse model of acute liver failure. SB216763 was used to inhibit the activity of GSK3β and PPARα siRNA was used to inhibit the expression of PPARα. Western blotting was used to measure the expression of PPARα protein. The changes in liver pathology were observed to evaluate liver injury, and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to assess liver function. Quantitative real-time PCR was used to measure the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12p40 (IL-12p40), and PPARα. A one-way analysis of variance was used for comparison of means between multiple groups; the least significant difference test was used for data with homogeneity of variance, and the Games-Howell method was used for data with heterogeneity of variance.@*Results@#In the mice with liver failure induced by D-GalN/LPS, GSK3β inhibition promoted the mRNA and protein expression of PPARα (F = 13.18 and 301.36, P = 0.00 and 0.00). In the mice with acute liver failure induced by D-GalN/LPS, GSK3β inhibition alleviated liver bleeding, inflammation, and necrosis and reduced the serum levels of ALT (F = 25.16, P = 0.000) and AST (F = 12.96, P = 0.001), as well as the mRNA expression of TNF-α (F = 32.17, P = 0.00), IL-1β (F = 11.57, P = 0.005), and IL-12p40 (F = 14.17, P = 0.015) in liver tissue. The inhibition of PPARα expression reversed the liver-protecting effect of GSK3β inhibition, which manifested as aggravation in liver bleeding, inflammation, and necrosis, increases in the serum levels of ALT (F = 25.16, P = 0.001) and AST (F = 12.96, P = 0.000), and an increase in the mRNA expression of TNF-α (F = 32.17, P = 0.00), IL-1β (F = 11.57, P = 0.024), and IL-12p40 (F = 14.17, P = 0.001) in liver tissue.@*Conclusion@#In mice with acute liver failure induced by D-GalN/LPS, the GSK3β-PPARα-inflammatory factor signaling pathway may play an important role. GSK3β inhibition has a protective effect in mice with acute liver failure possibly by activating the inhibitory inflammatory factor of PPARα.
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To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48 h was 80%. ALT and AST levels increased markedly at 4 h, but decreased significantly at 8 and 12 h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12 h. Clotting times, TNF-and IL-6 levels increased significantly, except for 12 h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochromeexpression peaked at 8 h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.
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Objective To investigate the protective effect of total flavones of Artemisia capillaris Thunb.on acute hepat-ic injury in rats. Methods Rats were randomly divided into blank control group,model control group, Yinzhihuang group,and groups of total flavones of Artemisia capillaris Thunb.(low,medium and high dose) in terms of 7-day different treatments.All rats except those in the blank control group were administrated with D-galactosamine hydrochloride ( 500 mg?g-1 , ip ) once at the sixth day.Then,concentrations of ALT and AST were detected 48 h later,and the liver samples were collected from each group for pathological examination. Results The serum ALT and AST in high-dose group of total flavones of Artemisia capillaris Thunb. was [(189.2±112.9) and (231.7±149.9) U?L-1],respectively,significantly lower than those in model control group ALT [(391.9±181.3) U?L-1] and AST [(403.9±133.8) U?L-1].Fragmented necrosis,fatty degeneration,inflammatory cells infil-tration and acidophilic degeneration of hepatic cells were improved to varying degrees in groups of total flavones of Artemisia capil-laris Thunb.compared with model control group.Fragmented necrosis of liver cells and steatosis occurred in 20 and 19 rats,respec-tively,in the model control group,while those appeared in 1 and 2 rats,respectively,in high-dose group of total flavones of Artemi-sia capillaris Thunb.. Conclusion Total flavones of Artemisia capillaris Thunb. are effective in protecting D-galactosamine hydrochloride-induced acute hepatic injury in rats.
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ABSTRACT:Objective To investigate changes in the neutrophils in rats with D-galactosamine (D-GalN)-induced acute liver failure (ALF)and to explore the therapeutic effect of interventions treatment of neutrophils on ALF.Methods Liver function,the expressions of inflammatory cytokines TNF-αand IL-1β,and the changes of neutrophils in the peripheral blood and the liver were observed in rats with D-GalN (intraperitoneal injection)-induced ALF.SD rats were randomly divided into three groups when treated with intervention of neutrophils:control group,ALF group (intraperitoneal injection of D-GalN),and treatment group (intravenous injection of anti-PMN serum via tail vein 24 h before modeling).Biochemical analysis was used to detect serum ALT,AST, TBIL and blood ammonia.Hematology analyzer was applied to analyze the number and percentage of peripheral blood neutrophils.The number of neutrophils in the liver was evaluated by immunohistochemistry.Liver RT-PCR was adopted to detect the mRNA expression of inflammatory cytokines TNF-αand IL-1β.Results We found that 6 h after D-GalN injection,serum ALT,AST,TBIL and blood ammonia in ALF rats were significantly increased (P <0.05).The mRNA expression levels of inflammatory cytokines TNF-αand IL-1βin the liver reached the peak at 6 h after modeling (P <0.001),and it was still notably higher at 24 h than before modeling (P <0.001 ).The number and percentage of peripheral blood neutrophils and the number of neutrophils in the liver were all markedly increased 12 h after modeling (P <0.001 ),and the increase continued at least until 24 h (P <0.001 ).24 h after intravenous injection of anti-PMN serum via tail vein,ALF rats had a distinct decrease in the number of peripheral blood neutrophils and neutrophils in the liver 24 h after modeling (P <0.001).Meanwhile,serum ALT,AST,TBIL and blood ammonia were all greatly decreased compared with those in ALF group (P <0.05);a significant reduction of hepatocyte apoptosis was observed.Also,the expressions of TNF-α and IL-1β in the liver were remarkably decreased after treatment (P <0.05).Conclusion Neutrophils accumulated in peripheral blood and liver of rats with D-GalN-induced ALF.The treatment of anti-PMN serum may have a therapeutic effect on liver function and immune microenvironment in ALF rats.
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Objective: To study the protective effects of Shufeng Jiedu Capsule on SD rats with acute liver injury induced by D- galactosamine/lipopolysaccharide (D-GalN/LPS). Methods: Eighty SD rats with average 250 g weight were randomly divided into four groups: the saline control group, LPS-induced model group, Shufeng Jiedu Capsule treatment group, and dexamethasone treatment group with 20 in each group. The rats in the saline group were ip injected with 0.5 mL of saline, other three groups were ip injected with D-GalN 700 mg/kg and LPS 10 μg/kg in order to induce the model of acute liver injury, The rats in dexamethasone treatment group were ip injected with dexamethasone 5 mg/kg, the rats in Shufeng Jiedu Capsule treatment group were ig fed a daily dose 100 mg/kg of Shufeng Jiedu Capsule. At day 1, 3, 5, and 7, five rats from each group were killed and their liver tissues were taken for HE staining to observe pathological manifestations; Enzyme-linked immunosorbent assay (Elisa) was taken for the following tests: the levels of alanine transaminase (ALT) and aspartate aminotransferase (AST), interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), Ornithine carbamoyltransferase (OCT), high-mobility group protein (HMGB-1), and glutathione s-transferase (GST) were determined. Results: Shufeng Jiedu Capsule could significantly alleviate the acute liver injury induced by D-GalN/LPS. Liver tissue of Shufeng Jiedu Capsule treatment group, compared to D-GaIN/LPS-induced model group, had lesser extent lesions. The levels of ALT and AST, IL-1β, TNF-α, OCT, HMGB-1, and GST were significantly lower than those of D-GalN/LPS model group (P 0.05). Conclusion: Shufeng Jiedu Capsule could inhibit the liver cell expression of IL-1β and TNF-α so as to reduce the acute liver injury induced by D-GalN/LPS.
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Objective To investigate the effect of restraint stress on liver injury in mice induced by D-galactosamine and lipopolysaccharide (D+L).Methods Normal BALB/c (B/c) mice were randomly divided into normal control, stress control, D+L group, and D+L+stress group.The mice of normal control group were bred routinely.The stress group was giv-en stress regularly and quantitatively.Mice in the D+L group were injected intraperitoneally with mixed solution of D-galac-tosamine and lipopolysaccharide at final concentration of 30 mg/mL and 2μg/mL, respectively, once every two days.The D+L+stress group was given equal stress as stress group after injection of D-galactosamine and lipopolysaccharide mixed solution. Eight weeks later, blood samples were collected to test serum aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue samples from all animals were collected to evaluate the degree of liver fibrosis by HE and Masson staining.Results At the 8th week, the ALT and AST values in the D+L+stress group were significantly reduced( P＜0.01) and AST/ALT value was significantly increased(P＜0.01)compared with that in the D+L group.For HE and Masson staining, disordered structure of hepatic lobules, nodular hyperplasia, and necrosis of epithelial cells were present in animals of the D+L group.However, no obvious pathological changes were observewd in the D+L+stress group.For fibrosis scores, the fibrosis grade in the D+L+stress group was significantly decreased than that of the D+L group (P＜0.05).Conclusions Constraint stress presents pro-tective effect on D-galactosamine and lipopolysaccharide induced liver injury in mice.
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Objective To establish a mouse model of acute liver failure induced by lipopolysaccharide /D-galac-tosamine ( LPS/D-GalN) .Methods The optimum dose of LPS/D-GalN was determined by i .p.injection of eight differ-ent doses of LPS and D-GalN into 40 female C57BL/6 mice and observation of their survival time .Then, 32 female C57BL/6 mice were i.p.injected with the optimal dose of LPS/D-GalN and sacrificed at 0, 1, 4, 8 hours after the injec-tion, 8 mice in each group.The control mice received saline injection .Hepatic changes were observed by pathology and se-rum ALT, IL-6, MCP-1 and TNF-αwere measured by biochemistry or flow cytometry .Results LPS (2.5 mg/kg) and D-GalN (0.3 g/kg) were determined as the optimal dose for the establishment of mouse model of acute liver injury .Com-pared with the control group , the hepatocellular damages were progressing in a positive correlation with the time course after LPS/D-GalN administration .The level of serum ALT was significantly increased after LPS/D-GalN administration ( P <0.001).The levels of inflammatory cytokines IL-6, MCP-1 and TNF-αwere increased and reached a peak at one hour after LPS/D-GalN administration and then decreased almost to that of the control group 8 hours later(P<0.001).Conclusions The mouse model of acute liver injury is successfully established by LPS /D-GalN administration , and provide an effective animal model for the study of pathogenic mechanisms of acute liver failure and evaluation of therapeutic drugs .
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Objective To research the method of Chronic hepatic injury modeling in mice induced by D -galactosamine and lipopolysaccharide combination . Methods Injected D-galactosamine ( 30 mg/mL ) and lipopolysaccharide ( 2μg/mL ) combination by intraperitoneal injection , two days at a time for 8 weeks .Monitored variation of diet and weight; detected serum level of alanine aminotransferase ( ALT ) and aspartate aminotransferase (AST), been put to death in mice and removed the liver tissue .strained hepatic tissue by the HE and Masoon dye to observe Liver tissue structure and cellular morphology and the degree of fibrosis .Results Lipopolysaccharide and D-galactosamine combination resulted in ALT rise , hepatocyte degeneration and necrosis ,collagen fiber hyperplasia obviously . Conclusion D-galactosamine and Lipopolysaccharide combination could induce mice chronic hepatic injury modeling .
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This study was aimed to observe effects of different doses of D-galactosamine (D-GalN) plus lipopoly-saccharide (LPS) and blood coagulation changes among rat model of acute liver failure, in order to establish an ideal model of acute liver failure in rats. SD rats were randomly divided into the control group, D-GalN high, medium and low dose groups, with 10 rats in each group. Except the normal group, rats in other groups were injected with D-GalN plus LPS at different doses to induce acute liver failure. The mortality of rats was observed. The liver function and blood coagulation were detected from rat serum at 0 h, 12 h, 24 h, 48 h, and 72 h. HE stain was used in the observa-tion of changes on liver pathological changes. The results showed that the mortality of D-GalN high, medium and low dose groups within 72 h were 60%, 30%, 10%, respectively. There were significant differences on the serum content level of ALT, AST, TBIL, PT, INR, FIB from different dose groups at different time points and the normal group (P<0.05). However, the comparison among D-GalN high, medium and low dose groups showed no statistical difference on ALT and AST; while there were statistical differences on TBIL, PT, INR and FIB (P < 0.05). It was concluded that coagulation index was more stable in the liver failure model. Through observation on the liver function, blood coagulation and pathological morphology, the model of acute liver failure induced with medium dose of D-GalN plus LPS in SD rats at 48 h was more similar to the clinical symptom of acute liver failure. Therefore, the medium dose was the ideal model inducing dose.
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Objective: The plant sphaeranthus amaranthoides Burm.f is used in the district thriunalveli in the treatment of various liver disorders. Methods: in the present study the ethanol extract from sphaeranthus amaranthoides was studied against the D-galactosamine hepatotoxicity. Results: significant hepatoprotective effect was obtained against liver damage induced by the D-galactosamine as evident from changed antioxidant enzymes like CAT, SOD, GPx, GST, GSH, G6PD and GR and a normal architecture of liver and mitochondria compared to toxin controls. Conclusions: the results indicate that ethanol extract of the sphaeranthus amaranthoides could be useful in preventing D-galatosamine induced liver injury.
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Objective: To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental animals. Methods: In the present study, in- vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D-Galactosamine (D-GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results: Obtained results demonstrated that the treatment with HCE signi-cantly (P<0.05-P<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, HCE signi-cantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that HCE attenuated the hepatocellular necrosis and led to reduction of in ammatory cells in-ltration. Conclusions: The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.
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AIM To evaluate the prevention and treatment of N-(2-mercaptopropionyl)-glycine sodium (MPG-Na) and tiopronin (MPG) on acute liver injury. METHODS The experimental mouse model of hepatotoxicity induced by D-galactosamine (Gal) was applied to investigate preventive and remedial effects. In the preventive experiment, the mice were ip administered with MPG-Na or MPG 37.5，75 and 150 mg·kg~(-1), respectively, for 7 d. Gal 800 mg·kg~(-1) was ip given into the mice 30 min after the last administration. In the remedial experiment, the mice were ip given Gal 800 mg·kg~(-1) and 30 min later followed by MPG-Na or MPG 37.5, 75 and 150 mg·kg~(-1) , respectively, for 2 d. The mice were euthanized and serum was prepared 24 h (pre-treatment) or 48 h (post-treatment) after Gal injection. The activities of serum glutamyl pyruvic transaminase (GPT) and glutamyl oxaloacetic transaminase (GOT), the contents of total protein (TP) and albumin (Alb), and the Alb/globulin (A/G) ratio were determined. The liver tissues were collected for histopathological assessment (HE staining) under light microscope. RESULTS Compared with normal control group, the activities of serum GPT and GOT in model group were significantly increased. The injuries such as fatty degeneration and liver cell necrosis were observed. Compared with model group, the activities of GPT and GOT in pre-treatment groups were obviously decreased in MPG-Na 150 mg·kg~(-1) group. In post-treatment groups, the activity of GPT decreased in 3 MPG-Na groups. The contents of TP, Alb and A/G ratio had little change. In addition, MPG-Na alleviated the injuries such as fatty degeneration and liver cell necrosis obviously. Compared with MPG, MPG-Na showed similar effect. CONCLUSION MPG-Na has an obvious protective effect against Gal-induced acute liver injury in mice and the efficiency is equivalent as MPG.
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Aim To investigate the effects of pyrrolidine dithiocarbamate (PDTC) on D-galactosamine/lipopolysaccharides (GalN/LPS)-induced acute apoptotic liver injury and its mechanism.Methods All mice were randomly divided into four groups.Mice in GalN/LPS group were co-injected with GalN (600 mg·kg~(-1),ip) and LPS (20 μg·kg~(-1), ip). Mice in PDTC+GalN/LPS group were injected with two doses of PDTC,one (100 mg·kg~(-1), ip) at 24 h before LPS and the other at 2 h before LPS (20 μg·kg~(-1), ip).Mice in control groups were treated with PDTC (100 mg·kg~(-1), ip) or saline. Ten mice in each group were observed for animal survival within 72 h after LPS treatment. Six mice in each group were sacrificed 1.5 h after LPS for collecting blood and isolating livers. The expression of hepatic TNF-α mRNA was determined by reverse transcription and polymerase chain reaction (RT-PCR). Hepatic nuclear factor-κB (NF-κB) binding activity was measured with electrophoretic mobility shift assay (EMSA).Twelve mice in each group were sacrificed 8 h after LPS treatment. Serum was collected for measurement of alanine aminotransferase (ALT) and hepatocellular apoptosis and histological examination.Results Co-injection of GalN and LPS markedly increased serum ALT activity. Histopathological examination of liver sections revealed that GalN/LPS induced hepatic congestion, necrosis and massive macrophages infiltration, and increased the number of TUNEL-positive cells in mouse liver.GalN/LPS treatments, led to 90% mortality within 72 h with severe congestion and necrosis in the liver of all the dead mice. PDTC pretreatment significantly inhibited GalN/LPS-induced hepatic NF-κB activation and TNF-α expression. In contrast, PDTC aggravated GalN/LPS-triggered hepatocellular apoptosis, increased serum ALT activity, exacerbated hepatic hemorrhage and necrosis, and accelerated death.Conclusion PDTC aggravates GalN/LPS-induced acute apoptotic liver injury via inhibiting NF-κB-mediated anti-apoptotic effects.
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Objective To investigate the correlation of oncosis and TNF-? in D-galactosamine (D-GalN) induced acute hepatic injury. Methods Acute hepatic injury model was induced by D-GalN in 24 SD rats, and 12 rats served as control. At 4, 8, 12, 16, 20, 24 h after intraperitoneal injection of D-GalN, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and the tumor necrosis factor-? (TNF-?) in liver tissue were measured. The pathological changes of liver and the oncosis of hepatocytes were observed by TEM. Results In acute hepatic injury, the levels of ALT, AST, TNF-? mRNA, OI were higher than that of control group (P
ABSTRACT
The enhancing potential of anatoxin a (AFB1) and D-galactosamine (DGA) on development of preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatic foci was examined using an in vivo mid-term assay system based on two-stage concept of hepatocarci-nogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) intraperi-toneally, and thereafter. with an interval of 2 weeks, AFBl at a graded concentration (0.06, 0.012, 0.0024, 0.00048, and 0.000096 mg/kg i.g.) and DGA (100 mg/kg i.p.) were administered for 6 weeks and then sacrificed. All rats were subjected to a two-thirds partial hepatectomy to induce a potent growth stimulus to DEN-altered hepatocytes at the week 3. The modifying potential was scored by comparing the number and the area (mm2) per cm2 of GST-P+ foci in the liver with those of the corresponding control group given DEN alone. AFBl (at a graded concentration between 96 ng/kg and 60 microgram/kg) exerted a strong promoting effect oil induction of GST-P+ foci with both the number and the area. The logarithmic dose of AFBl and the potency to promote hepatocarcinogenesis were in dose-dependent relationship. DGA, a known necrogenic chemical to cause periportal necrosis and stimulate hepatocellular proliferation. also revealed the increase in the area of GST-P+ foci. although its enhancing potentia1 was 1ess profound than that of AFBl. The results suggest that DGA is also a useful proliferative stimulus m improve the medium-termdetection of unknown carcinogens.