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The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1β) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1β and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.
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Animals , Mice , Chemical and Drug Induced Liver Injury , Drug Therapy , Cytokines , Metabolism , Eleutherococcus , Chemistry , Liver , Mice, Inbred BALB C , NF-kappa B , Metabolism , Peptides, Cyclic , Polysaccharides , Pharmacology , Random Allocation , Signal TransductionABSTRACT
AIM:To investigate the influence of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury.METHODS:Fifty SD rats were randomly divided into control group,model group,low,middle and high experimental group of Jiedu hugan granule (2.7,5.4,and 10.8 g/kg).All the groups excepted the control group received intraperitoneal injections of 0.5 mL pig serum for each to establish immunological liver injury model.The experimental group was irrigated ltime/d,continuous dosing for 14 d.The liver tissue and small intestinal tissue pathological changes were observed by HE staining,the serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were detected,and the expression of liver tissue TNF-α and small intestine tissue occludin-5 were detected by immunohistochemical method.RESULTS:The model group liver tissue showed accumulation of fat cells,liver cells enlargement,disorganized liver and associated with inflammatory cells infiltration;the experimental group liver cell morphological ruled,hepatic cords in alignment and inflammatory cells infiltration significantly decrease.The model group small intestinal mucosa villi showed atrophy,fall off of epithelial cell,edema,large number of inflammatory cells infiltration;the experimental group showed closelyknitted small intestinal mucosa villi,relieve edema,and no obvious infiltration of inflammatory cells.The levels of ALT,AST,LDH and TNF-α in experimental group were statistically lower than the model group,and the levels were statistically reduce with the dose of jiedu hugan granule increased.The levels of occludin-5 in experimental group were statistically highter than those of the model group,and the levels of occludin-5 were statistically increase with the dose of Jiedu hugan granule increased,the differences were statistically significant (P ＜ 0.05).CONCLUSION:Jiedu hugan granule can improve the organizational structure of liver and small intestine,protect the damage of liver,reduce inflammation,and maintain small intestine mucosal barrier function.
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OBJECTIVE:To investigate the protective effect and mechanism of Wei medicine Cichorium glandulosum 95% eth-anol extract(CG-I)on immunological liver injury in mice,and provide reference for post-screening its effective site. METHODS:60 mice were randomly divided into blank control group(normal saline),model group(normal saline),positive control group(Di-ammonium glycyrrhizinate,100 mg/kg) and CG-I high-dose,medium-dose,low-dose groups (calculated by crude drugs as 200, 100,50 g/kg),10 in each group,intragastrically administrated once every day,for 10 d. After 1 h of last administration,except for blank control group,mice in other groups were intravenously injected Con-A in tail to induce immunological liver injury. After 8 h of modeling,tumor necrosis factor α(TNF-α),interferon γ(IFN-γ),interleukin 1β(IL-1β)contents in serum were detected;liver and spleen indexes were calculated. The pathological changes in liver tissue were observed,and aspartate aminotransferase(AST), alanine aminotransferase (ALT), glutathione S-transferase (GST), alkaline phosphatase (AKP), total superoxide dismutase (T-SOD),malondialdehyde(MDA)levels in liver tissue were detected. RESULTS:Compared with blank control group,TNF-α, IFN-γ,IL-1β contents in serum in model group were significantly increased;liver,spleen indexes and AST,ALT,GST,AKP, T-SOD levels in liver tissue were significantly increased;and MDA level in liver tissue was significantly reduced,with statistical significances(P<0.05 or P<0.01);liver of mice in model group was cluttered,showing swelling,necrosis and other diseases in liver cells. Compared with model group, except that AST, ALT,AKP levels in liver tissue in CG-I low-dose group and MDA, IFN-γ contents in serum in CG-I medium-dose, low-dose groups had no significant decrease, other indexes were significantly improved (P<0.05 or P<0.01);and patho-logical changes in liver tissue were relieved to varying degrees. CONCLUSIONS:CG-I shows protective effect on Con-A-in-duced immunological liver injury in mice,especially the high dose and medium dose. The mechanism may be associated with its an-ti-oxidation and anti-inflammatory effects.
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Aim To explore the protective effects and underlying mechanisms of Liu weiwuling Tablets (LW-WL)in concanavalin A (ConA)induced acute immu-nological liver injury in mice.Methods Mice were randomly divided into control,model,Bicyclol,LW-WL low dose (8 g·kg-1 )and LWWL high dose (16 g ·kg-1 )group.The medicattion was performed once daily for seven consecutive days,then the model of im-munological liver injury was prepared by intravenous injection of ConA (15mg·kg-1)in the tail of mice in each group except for the control group one hour after the last treatment.The pathological changes of liver tissues of mice were evaluated by HE staining with, and the levels of alanine amino transferase (ALT),as-partate aminotransferase (AST),and total bilirubin (TBIL)in serum were analyzed by colorimetric meth-od;the level of interleukin 12 (IL-12 ),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleu-kin 4 (IL-4)and interleukin 10 (IL-10)in liver was measured by real-time quantitative polymerase chain reaction (RT-qPCR);the changes of Th1 (IFN-γ) and Th2 (IL-4)cells were observed by flow cytometric (FCM)analysis;the expression of Th1/Th2 transcrip-tion factor T-bet/GATA-3 in liver tissue was detected by Western blot.Results Compared with normal con-trol group,the serum ALT,AST and TBIL were signif-icantly increased in model group, the pathological damage of the liver tissue was severe,and the necrosis and apoptosis of hepatic cells were large, which showed that the model was successful .Compared with model group,both low and high dose of LWWL could significantly reduce ALT,AST,TBIL levels in serum induced by ConA;Th1 cells in the spleen decreased, while Th2 cells increased;the expressions of IL-12, IFN-γand TNF-αmRNA were significantly inhibited with IL-4 and IL-10 mRNA expression elevated in mouse liver tissue;the expression of GATA-3 protein was up-regulated,T-bet protein expression showing no significant changes.Conclusion LWWL could regu-late Th1/Th2 balance,thus inhibiting the acute immu-nity hepatic injury induced by ConA.
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OBJECTIVE To evaluate the protective effect of Agaricus bisporus intracellular polysaccharides(IPS) and exopolysaccharides (EPS) on immunological liver injury induced by concanavalin A (Con A). METHODS Mice were pretreated with IPS and EPS (100, 200 and 400 mg kg- 1, ig) daily for 12 d. Immunological liver injury was induced by Con A 25 mg·kg-1 byinjection via the tail vein of mice.Eight hours after injection of Con A, the indexes of the liver, spleen and thymus, serum level of glutamicpyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), tumor necrosis factor-α (TNF-α) and interferon- γ (IFN- γ), splenic lymphocyte percentages of CD4 + and CD8 + , and liver homogenate content of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Liver pathological changes were observed by HE staining. RESULTS Compared with normal group, the autoimmune liver injury in mice induced by Con A resulted in an increase in the liver index (P<0.01) , spleen index (P<0.01), the activity of GPT (P<0.01) and GOT (P<0.01), the content of TNF- α (P<0.01) and IFN- γ (P< 0.01), and the level of MDA (P<0.01), but a decrease in the thymus index (P<0.01), the percentage of CD4+ (P<0.01) , the ratio of CD4+/CD8+ (P<0.01), and SOD activity (P<0.01). Compared with model group, treatment with IPS (200 and 400 mg·kg-1) and EPS (200 and 400 mg·kg-1 ) respectively resulted in an increase in the thymus index (P<0.01) but in a decrease in the liver index and spleen index (P<0.01). Similarly, the activity of GOT and GPT was decreased obviously (P<0.01), and the content of TNF-α and IFN-γ in IPS and EPS 200 and 400 mg·kg-1 groups was decreased. Compared with model group, the activity of SOD in IPS and EPS (200 and 400 mg·kg- 1) group was increased (P<0.01) while MDA was decreased (P<0.01). Moreover, the percentage of CD4 + Iymphocytes decreased (P<0.01), whereas no significant difference was found in the ratio of CD4 +/CD8 + .Pathological changes of the liver were observed under a microscope. Pretreatment with IPS and EPS could effectively reduce the liver injury induced by Con A. CONCLUSION IPS and EPS have certain protective effect on immunological liver injury, which may be related to their ability to clean up free radicals, control lipid peroxidation and regulate the balance of the immune system.
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Aim To investigate the effect of Zhizi Baipi soup and its disassembled prescription containing Zhizi on protecting concanavalin (ConA)-induced immuno-logical liver injury in mice and explore the possible protective mechanism.Methods The model of mouse immunological liver injury induced by (ConA,20 mg ·kg -1 )was used to observe the effects of Zhizi Baipi soup and its disassembled prescription containing Zhizi by gavage administration.Results Zhizi Baipi Soup and its disassembled prescription containing Zhizi were able to reduce the level of serum ALT,AST and MDA content,improve liver tissue SOD activity and reduce the expression of NF-κB-p65 and NF-κB-p-p65,in which all parties of Zhizi Baipi Soup Group had best effect on immunological liver injury in mice.Conclu-sion Zhizi Baipi Soup and its disassembled prescrip-tion containing Zhizi have remarkably protective effect on ConA-induced immunological liver injury in mice, and the potential mechanism may be related to the reg-ulation of the immune response pathway.
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Objective To study the impact of thalidomide on the immunological liver injury animal model in mice .Methods The immunological liver injury animal model was established in mice by injection of Bacillus Calmette-Guerin(BCG) and lipopolysaccha-ride (LPS) .These mice were randomly divided into five groups :normal control group ,model group ,positive medicine group (cyclo-phosphamide 100 mg/kg ,ip ,1 ,3 and 5 days after inoculation) ,Salle Lenalidomide (low ,medium and high dose group) ,and all of the mice were continuously administrated for 15 days ,the index of liver and spleen were detected ;Spectrophotometric was used to detect the levels of serum ALT ,AST and the content of MDA ,SOD ,GSH-Px in liver homogenates ;HE stain was used to exanimate the liver histopathology for the pathological grading and scoring of liver injury ;ELISA was used to measure the expression of TGF-β1 , IL-6 in liver homogenates ;RT-PCR was used to detect the mRNA expression of TNF-αin liver tissue .Results Thalidomide can re-duce the ALT ,AST ,MDA contents in these mice model ,increase the SOD ,GSH-Px activities and significantly reduce the index of liver and spleen of the mice with immunological liver injury (P<0 .05 or P<0 .01);also it can reduce the TGF-β1 ,IL 6 expression , inhibit TNF-αmRNA expression ,and reduce the damage degree of liver pathology .Conclusion Thalidomide can relieve the liver fi-brosis after immunological liver injury ,playing a protective role in the immunological liver injury mice model ,and its mechanism may be related to the inhibition of TGF-β1 and TNF-αexpression and the balance of cytokines .
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Objective: To study the protection of the terpenes and flavonoids from Chrysanthemi Indici Flos (CIF) on immunological liver injury (ILI) induced by concanavalin A (Con A) in mice. Methods: Mice were divided into control, model, CIF-A (terpenes), CIF-B (terpenes and flavonoids), and CIF-C (flavonoids in high-, mid-, and low-dose) groups, and with Bifendate Pills as positive control group. Mice were ig administered with the three extracts from CIF each once in the morning and afternoon of the first day and the next afternoon, then once daily for consecutive 7 d. The model of ILI was prepared by iv injection of Con A in the tail of mice in each group except the control group. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), inferon-α (TNF-α), and interferon-γ (IFN-γ) in serum of mice were analyzed, the level of MDA in liver was measured, and the histopathological changes of hepatic tissue were observerd. Results: Compared with the model group, CIF-A and CIF-B could obviously inhibit the increased levels of AST, ALT, and TNF-α in serum, while CIF-C could mainly reduce the levels of AST, ALT, IFN-γ, and CIF-B could decrease the level of MDA in the liver tissue with the significant amelioration of liver lesions. The effect of CIF-B was stronger than that of CIF-C and CIF-A. Conclusion: Terpenes and flavonoids from CIF have a certain protective effect on the liver of mice with ILI induced by Con A, and CIF-B has stronger effect.
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OBJECTIVE: To investigate the pharmacokinetics of irinotecan (CPT-11) in SD rats with immunological liver injury. METHODS: The animal model of immunological liver injury was established by intraperitoneal injection of lipopolysaccharide (LPS) plus Bacille-Calmette-Guerin (BCG) in rats. Rats were randomly divided into two groups; normal control group and immunological liver injury model group. The two groups were injected with CPT-11 (20 mg · kg-1) via tail vein and plasma concentrations of CPT-11 and its metabolite SN-38 were determined by HPLC. Pharmacokinetical parameters were calculated. RESULTS: Compared with the normal control group, AUC0-24h, AUC0-∞ and ρmax of CPT-11 in immunological liver injury rats were increased significantly (P < 0.05), but AUC0-24h, AUC0-∞ and ρmax of SN-38 were decreased significantly (P < 0.05). CONCLUSION: Under the state of immunological liver injury, the hydrolysis of CPT-11 is inhibited significantly. The underlying mechanism may be related to the down-regulation of the expression of carboxylesterase 2 by LPS. Copyright 2012 by the Chinese Pharmaceutical Association.
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OBJECTIVE:To investigate the effects of Yinzhihuang oral solution on immunological liver injury (ILI). METHODS:Male mice were randomly divided into blank group (normal saline), model group (normal saline), bifendate group(150 mg?kg-1),high dosage group (Yinzhihuang oral solution 30 mL?kg-1), medium dosage group (Yinzhihuang oral solution 20 mL?kg-1) and low dosage group (Yinzhihuang oral solution 10 mL?kg-1). All rats were given medicine via i.g. gtt for 10 days. ILI model was induced by intravenous injection of bacillus calmette-guerin vaccine (BCG) and lipopolysaccharides (LPS). The content of IL-6 and TNF-? were detected by ELISA. The levels of ALT, AST, MDA and SOD were detected by spectrophotometer. RESULTS:Compared with model group, the level of ALT, AST, MDA, IL-6 and TNF-? were decreased significantly in high dosage, medium dose and low dosage groups (P
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Aim To investigate the effect of Dicranostiga Leptodu (Maxim) Fedde (DLF) on experimental liver injury induced by Calmette Guerin bacillus vaccine (BCG) and Lipopolysaccharide (LPS) in mice. Methods Experimental liver injury was induced by Calmette Guerin bacillus vaccine and Lipopolysaccharide in male mice by injecting via tail vein (50 ?g?kg -1 ), and administering LPS (10 ?g?mouse -1 ) 10 d later. Therapeutic groups were given respectively with DLF (0 5,1 0,2 0 g?kg -1 ) before administration of LPS. The level of ALT, AST and LDH and the concentration of ALB and GLB in serum were measured by automatic biochemistry analyzer, and MDA in liver plasma was measured by TBA method and the level of SOD was measured by pyrogallol auto oxidation method. Pathological morphological changes in liver tissue were observed. Results The three experimental groups were found with significant decrease in the elevation of serum GPT and LDH level and the content of MDA in the liver plasma. The liver tissue damages were also ameliorated. Conclusion DLF has protective effect against the experimental liver injury induced by BCG and LPS in mice.
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AIM: To investigate the prophylactic effect of melatonin (MT) on immunological liver injury. METHODS: The model of mouse immunological liver injury was induced by injection of bacillus calmette guerin (BCG) and lipopolysaccharide (LPS) from tail vein. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) level in plasma, malondiadehyde (MDA) content and superoxide dismutase (SOD) activity in liver homogenate were assayed with different methods; Tumour necrosis factor-α (TNF-α) activity was determined by method of L929 cells line; Interleukin-1 activity was determined by method of thymocytes proliferation. RESULTS: Immunological liver injury was successfully induced by BCG + LPS. MT (0.25, 1,4 mg·kg-1) was found to decrease significantly the serum transaminase (ALT,AST) activities. However, MT at the dose of 1 mg·kg-1 was the most effective among the three doses. MT also decreased MDA content and improved reduced SOD level in liver homogenate. Furthermore, MT significantly reduced TNF-α, NO and IL-1 levels in serum. CONCLUSION: MT shows significant protective action on immunological liver injury in mice.
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AIM: To study the protect effects of paecilomyceps sinensis sp nov (CN-802) on immunological liver injury in mice which induced by BCG+LPS. METHODS: LPS was injected into mice via the tail vein pretreated with BCG. The activity of serum ALT, the weighing indexes of liver and spleen, the levels of LPO in serum and hepatic tissues, and the numbers of subgroup of T lymphocyte were determined respectively. RESULTS: CN-802 at dose of 1.0 g?kg -1?d -1 decreased the serum ALT level, the liver and spleen-enlarged index and the LPO levels in serum and hepatic tissues. Analysis of CD_4/CD_8 in the peripheral blood showed that CN-802 increased the number of CD_4 lymphocyte and the ratio of CD_4/CD_8. CONCLUTION: Pretreatment with CN-802 prevents the immunological liver injury induced by BCG+LPG, and the effect of CN802 may be related with the regulatory of immune cells.
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Aim To study effects of N-Acetylcysteine on Lipopolysaccharide-induced immunological liver injury in mice. Methods A model of immunological liver injury was induced by injection of LPS in mice primed with BCG. NAC was administered in two different modes. In mode A, mice were pretreated with two doses of NAC before LPS, one (150 mg?kg-1, ip) at 4 h before LPS and the other (150 mg?kg-1, ip) at 15 min before LPS. In mode B, mice were administered with two doses of NAC after LPS, one (150 mg?kg-1, ip) injected immediately after LPS and the other (150 mg?kg-1, ip.) injected 4 h after LPS. Some mice were sacrificed at 1.5 h after LPS and livers were dissected for total RNA extraction. Hepatic TNF-? mRNA level was determined by using RT-PCR. The remaining mice were sacrificed at 8 h after LPS. Blood serum was collected for measurement of alanine aminotransferase (ALT) and nitrate plus nitrite. Livers were dissected for measurements of GSH and lipid peroxidation. Results Pretreatment with NAC significantly alleviated LPS-induced increase in ALT activity, attenuated LPS-induced hepatic GSH depletion and TNF-? mRNA expression in mice primed with BCG. However, NAC had no effects on LPS-induced NO production and hepatic lipid peroxidation. By contrastwith pretreatment, posttreatment with NAC had littleeffects on LPS-induced immunological liver injury and in fact aggravated LPS-induced NO production and hepatic GSH depletion and increased LPS-induced mortality in mice primed with BCG. Conclusion NAC has a dual effect on LPS-induced immunological liver injury. Pretreatment with NAC protects against LPS-induced immunological liver injury via counteracting LPS-induced oxidative stress and TNF-? mRNA expression in mouse liver. However, when administered after LPS, NAC behaves as a prooxidant and aggravates LPS-induced mortality in mice primed with BCG.
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Objective To study the regulatory effect of cefodizime on the T-lymphocyte subsets of peripheral blood in mice with immunological liver injury.Methods The mouse model of immunological liver injury was induced by Bacillus Calmette Guerin and Lipoposaccharide.The study was conducted by using completely random design.The mice with immunological liver injury were divided into thymosin group,cefodizime high-,medium-,low-dose groups,ceftriaxone group and the normal saline group.The six groups were continuously administered agents respectively for 7 days,and T-lymphocyte subsets of peripheral blood in mice were determined and contrasted with those of the normal mice treated with normal saline on the 7th day.Flow cytomytry was used to determine the effects of cefodizime on T-lymphocyte subsets of peripheral blood in mice by using immuno-fluorescence technique.Results The immunological liver injury mice were deficient because their CD3+(%),CD4+(%),CD8+(%) and the ratio of CD4+CD8+ were lower than those of the normal mice.Cefodizime effectively increased CD3+(%),CD4+(%) and the ratio of CD4+CD8+ of the mice with immunological liver injury.Conclusion Cefodizime effectively improves the immune function of the host by regulating the balance between CD4+ cell and CD8+ cell.