Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

Acetaminophen(APAP),the most frequently used mild analgesic and antipyretic drug worldwide,is implicated in causing 46%of all acute liver failures in the USA and between 40%and 70%in Europe.The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine(NAC);however,its efficacy is limited in cases of advanced liver injury or when administered at a late stage.In the current study,we discovered that treatment with a moderate intensity static magnetic field(SMF)notably reduced the mortality rate in mice subjected to high-dose APAP from 40%to 0%,proving effective at both the initial liver injury stage and the subsequent recovery stage.During the early phase of liver injury,SMF markedly reduced APAPinduced oxidative stress,free radicals,and liver damage,resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione(GSH).During the later stage of liver recovery,application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation.Moreover,the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery,even 24 h post overdose,when the effectiveness of NAC alone substantially declines.Overall,this study provides a noninvasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose.Of note,this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP,and potentially other toxic overdoses.

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.

Co-administration of cyclosporine A alleviates thioacetamide-induced liver injury

AIM: To investigate the effects of cyclosporine A (CsA)on thioacetamide (TAA)-induced liver injury.METHODS: CsA was co-administrated (7.5 μg/kg body weight per day, i.p.) into rat to investigate the role of CsA on TAA-(200 mg/kg body weight per 3 d for 30 d, i.p.)induced liver injury.RESULTS: The data show that TAA caused liver fibrosis in rat after 30 d of treatment. CsA alleviates the morphological changes of TAA-induced fibrosis in rat liver. The blood glutamyl oxaloacetic transaminase (GOT)/glutamyl pyruvic transaminase (GPT) in the TAA-injury group is elevated compared to that of the normal rat. Compared with the TAA-injury group, the blood GOT/GPT and TGFβ1 (by RT-PCR analysis) are reduced in the CsA plus TAA-treated rat. The level of the transforming growth factor receptor I (TGFβ-R1) in the CsA plus TAA-treated group shows higher than that in the TAA only group, but shows a lower level of the fibroblast growth factor receptor 4 (FGFR4)in the CsA plus TAA-treated group, when using the Western blot analysis. After immunostaining of the frozen section,TGFβ-R1 and FGFR4 are more concentrated in rat liver after CsA plus TAA injury.CONCLUSION: This result suggests that CsA has an alleviated effect on TAA-induced liver injury by increasing the multidrug resistance P-glycoprotein and could be through the regulation of TGFβ-R1 and FGFR4.

Liuweiwuling tablets attenuate acetaminophen-induced acute liver injury and promote liver regeneration in mice

AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice.A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group(control group) and a Liuweiwuling tablet group.Mice were given Liuweiwuling tablets or a vehicle(PBS) orally prior to the administration of acetaminophen.Serum alanine aminotransferase(ALT) and aspartate aminotransaminase(AST) levels were measured at different time points within one week,and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury.Serum inflammatory cytokines,such as high mobility group box protein B1(HMGB1),tumor necrosis factor(TNF)-α and interleukin IL-1b,were detected using an ELISA method according to the manufacturer's instructions.Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining.Expression of proliferating cell nuclear antigen(PCNA) in liver tissue was determined by Western blot analysis.The m RNA levels of hepatocyte proliferation markers(PCNA,Cyclin D1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6,12 and 24 h compared to that of the control group(654.38 ± 120.87 vs 1566.17 ± 421.64,1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37,P < 0.01).Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group(23.49 ± 3.89 vs58.6 ± 3.65,61.62 ± 13.07 vs 27.32 ± 5.97,P < 0.01).Furthermore,serum TNF-α and IL-1b levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group(299.35 ± 50.61 vs 439.03 ± 63.59,57.42 ± 12.98 vs 160.07 ± 49.87,P < 0.01).Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury,but was almost abolished in the Liuweiwuling tablet group.The expression levels of PCNA and Cyclin D1 were up-regulated in liver tissue in the Liuweiwuling tablet group(321.08 ± 32.87 vs 157.91 ± 21.52,196.37 ± 25.39 vs 68.72 ± 11.27,P < 0.01); however,expression of p21 in liver tissue was downregulated compared to that of the control group(40.26 ± 9.97 vs 138.24 ± 13.66,P < 0.01).CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine(HMGB1,TNF-α and IL-1b) levels and promoting liver regeneration.

Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury

AIM: To investigate the effects of broccoli sprout extract(BSEx) on liver gene expression and acute liver injury in the rat.METHODS: First, the effects of BSEx on liver gene expression were examined. Male rats were divided into two groups. The Control group was fed the AIN-76 diet, and the BSEx group was fed the AIN-76 diet containing BSEx. After a 10-d feeding period, rats were sacrificed and their livers were used for DNA microarray and realtime reverse transcription-polymerase chain reaction(RT-PCR) analyses. Next, the effects of BSEx on acute liver injury were examined. In experiments using acute liver injury models, 1000 mg/kg acetaminophen(APAP) or 350 mg/kg D-galactosamine(D-Gal N) was used to induce injury. These male rats were divided into four groups: Control, BSEx, Inducer(APAP or D-Gal N), and Inducer+BSEx. The feeding regimens were identical for the two analyses. Twenty-four hours following APAP administration via p.o. or D-Gal N administration via i.p., rats were sacrificed to determine serum aspartate transaminase(AST) and alanine transaminase(ALT) levels, hepatic glutathione(GSH) and thiobarbituric acid-reactive substances accumulation and glutathioneS-transferase(GST) activity. RESULTS: Microarray and real-time RT-PCR analyses revealed that BSEx upregulated the expression of genes related to detoxification and glutathione synthesis in normal rat liver. The levels of AST(70.91 ± 15.74 IU/m L vs 5614.41 ± 1997.83 IU/m L, P < 0.05) and ALT(11.78 ± 2.08 IU/m L vs 1297.71 ± 447.33 IU/m L, P < 0.05) were significantly suppressed in the APAP + BSEx group compared with the APAP group. The level of GSH(2.61 ± 0.75 nmol/g tissue vs 1.66 ± 0.59 nmol/g tissue, P < 0.05) and liver GST activity(93.19 ± 16.55 U/g tissue vs 51.90 ± 16.85 U/g tissue, P < 0.05) were significantly increased in the APAP + BSEx group compared with the APAP group. AST(4820.05 ± 3094.93 IU/m L vs 12465.63 ± 3223.97 IU/m L, P < 0.05) and ALT(1808.95 ± 1014.04 IU/m L vs 3936.46 ± 777.52 IU/m L, P < 0.05) levels were significantly suppressed in the D-Gal N + BSEx group compared with the D-Gal N group, but the levels of AST and ALT in the D-Gal N + BSEx group were higher than those in the APAP + BSEx group. The level of GST activity was significantly increased in the D-Gal N + BSEx group compared with the D-Gal N group(98.04 ± 15.75 U/g tissue vs 53.15 ± 8.14 U/g tissue, P < 0.05).CONCLUSION: We demonstrated that BSEx protected the liver from various types of xenobiotic substances through induction of detoxification enzymes and glutathione synthesis.

Protective effect of fufanghuangqiduogan against acute liver injury in mice

AIM: To study the effects and possible mechanisms of fufanghuangqiduogan (FFHQ) in mice with acute liver injury (ALI). METHODS: ALI was successfully induced by injecting carbon tetrachloride (CCl4) intra peritoneally and by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice, respectively. Each of the two model groups was divided into normal group, model group, FFHQ (60, 120 and 240 mg/kg) treatment groups, and bifendate treatment group. At the end of the experiment, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in liver homogenate were measured by biochemical methods. The activities of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were determined by radio-immunoassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS: In the two models of ALI, FFHQ (60, 120, 240 mg/kg) was found to significantly decrease the serum transaminase (ALT, AST) activities. Meanwhile, FFHQ decreased MDA contents and upregulated the lower SOD and GSH-px levels in liver homogenate. Furthermore, in immunologic liver injury model, FFHQ decreased levels of TNF-α and IL-1 in serum. Histologic examination showed that FFHQ could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. CONCLUSION: FFHQ had protective effect on liver injury induced by either CCl4 or BCG+LPS in mice, and its mechanisms were related to free radical scavenging, increasing SOD and GSH-px activities and inhibiting the production of proinflammatory mediators.

Role of the^(13)C-methacetin breath test in the assessment of acute liver injury in a rat model

AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine(D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group(n = 8) and five model groups(each n = 8), and acute liver injury was assessed at different time points(6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green(ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT(Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman'scorrelation analysis.RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score(r = 0.493, P < 0.05; r =-0.731, P < 0.01; r =-0.618, P < 0.01; r =-0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection(3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.

Protective Effect of Procyanidin B2 on Acute Liver Injury Induced by Aflatoxin B1 in Rats

Objective This study aimed to explore the protective effect of procyanidin B2(PCB2)on acute liver injury induced by aflatoxin B1(AFB1)in rats.Methods Forty Sprague Dawley rats were randomly divided into control,AFB1,AFB1+PCB2,and PCB2 groups.The latter two groups were administrated PCB2 intragastrically(30 mg/kg body weight)for 7 d,whereas the control and AFB1 groups were given the same dose of double distilled water intragastrically.On the sixth day of treatment,the AFB1 and AFB1+PCB2 groups were intraperitoneally injected with AFB1(2 mg/kg).The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide(DMSO).On the eighth day,all rats were euthanized:serum and liver tissue were isolated for further examination.Hepatic histological features were assessed by hematoxylin and eosin-stained sections.Weight,organ coefficient(liver,spleen,and kidney),liver function(serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total bilirubin,and direct bilirubin),oxidative index(catalase,glutathione,superoxide dismutase,malondialdehyde,and 8-hydroxy-2′-deoxyguanosine),inflammation factor[hepatic interleukin-6(IL-6)m RNA expression and serum IL-6],and bcl-2/bax ratio were measured.Results AFB1 significantly caused hepatic histopathological damage,abnormal liver function,oxidative stress,inflammation,and bcl-2/bax ratio reduction compared with DMSO-treated controls.Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB1.Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB1.

Protective effect of glutamine in critical patients with acute liver injury

BACKGROUND：Glutamine （Gin） supplementation is known to decrease oxidative stress and inflammatory response, enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was undertaken to evaluate the relationship between the effect of early parenteral glutamine （Gin） supplement on acute liver injury （ALl） and heat shock protein 70 （HSP-70） expression in critical patients. METHODS：Forty-four patients who had been admitted to the emergency intensive care unit （EICU） of Nanjing First Hospital Affiliated to Nanjing Medical University were randomly divided into a control group （n=22） and a Gin group （n=22）. The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gin 0.4 g/kg per day was given for 7 days in the Gin group. Serum HSP-70 and Gin were measured at admission and at 7 days after admission. Serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, and total bilirubin （TBiL）, serum levels of HSP-70 and Gin, mechanical ventilation （MV） time, ICU stay, peripheral blood of TNF-α, IL- 6, CD3, CD4 and CD4/CD8 levels were also measured in the two groups. RESULTS： In the Gin group, the levels of serum HSP-70 and Gin were significantly higher after Gin treatment than those before the treatment （P〈0.01）. HSP-70 level was positively correlated with the Gin level in the Gin group after administration of parenteral Gin （P〈0.01）. The levels of serum ALT, AST, TBiL and TNF-a, IL-6 were lower in the Gin group than in the non-Gin group （P〈0.01）. MV time and ICU stay were significantly different between the two groups （P〈0.05）. The levels of CD3, CD4 and CD4/ CD8 were significantly higher in the Gin group than in the control group after treatment （P〈0.05）. CONCLUSION：Parenteral Gin significantly increases the level of serum HSP70 in critically ill patients. The enhanced expression of HSP70 is correlated with improved outcomes of Gin-treated patients with acute liver injury.

Effects of Salmonella infection on hepatic damage following acute liver injury in rats

BACKGROUND： Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS： Oral supplementation with Salmonella enterica serovar enteritidis（S. enteritidis） was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury.RESULTS： The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury（P〈0.01）; The peyer＇s patch CD3＋ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group（P〈0.05）. S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation.CONCLUSIONS： Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe.Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

The Protective Effect of Arabinose + Mannose on Mice with Acute Liver Injury Induced by CCl_4 and Its Mechanism

[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mice were selected and then randomly divided into normal control,model group and positive group( bifendate 120 mg/kg),high-dose arabinose + mannose group( 800 mg/kg),middle-dose arabinose + mannose group( 400 mg/kg) and low-dose arabinose + mannose group( 200 mg/kg),each group had 10 mice,which were fed adaptively for 1 week. Except normal control group and model group,each treatment group was given medicine by gavage once a day and lasted for7 days according to the dosage of 20 ml/kg. After the last drug,except normal control group,the mice of other groups were injected 10 ml/kg0. 12% CC14 peanut oil through enterocoelia,thereby establishing acute liver injury model. The mice were fasted but not water for 24 h,after that,blood was sampled from mice eyes,then dissected rapidly. The activities of ALT and AST in the serum were determined,the expression levels of TNF-α,IL-1β and IL-6 from the hepatic tissues were detected by enzyme-linked immunosorbent assay( ELISA); then after HE dye,the changes of liver histopathology were observed. [Results]Compared with CCl_4 model,the activities of ALT and AST from the serum of mice from high-dose and middle dose groups decreased significantly( P < 0. 01); the contents of TNF-α,IL-1β and IL-6 from the hepatic tissues of mice decreased significantly( P < 0. 01); the pathological section showed that the liver injury of mice from the combined drug groups showed alleviating trend to varying degrees,in which the liver injury of mice from the high-dose group was the best. [Conclusions] Arabinose + mannose has an obvious protective effect on mice with acute liver injury induced by CCl_4,and its mechanism may relate to anti-inflammatory.

Protective effects of NYG-1 on CCl4-induced acute liver injury in rats

OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly divided into six groups with 8 in each group,normal group,model group,positive control group(silibinin),low-,medium-and high-dose NYG-1 group.Silibinin was given orally to rats in the positive control group,NYG-1(high-,medium-and low-dose)was given orally in the high-,medium-and low-dose NYG-1group,respectively.Those rats were administered appropriately according to the group once daily for seven consecutive days.On the seventh day,rats were treated with 10% CCl4(10mL·kg-1 of0.1% CCl4 solution in olive oil)intraperitoneally injecting(ip)to induce acute liver injury,except the normal group.At 16 h after CCl4 treatment,rats were weighed,then anaesthed with ether,the blood and liver were collected.Serum ALT,AST,LDH and ALP were measured.MDA content and SOD activity in liver homogenate were detected.The histopathological changes of liver were observed by H&E staining.RESULTS Acute liver injury model was established successfully in rats by intraperitoneally injecting CCl4.Pretreatment with medium and high dose NYG-1 decreased the increase of ALT,AST and MDA induced by CCl4,but it had no influence on serum LDH,ALP level and SOD activity in the liver homogenate.CONCLUSION The obtained results suggest that oral administration of NYG-1 hasve the protective effects against CCl4-induced acute hepatic injury in rats,Its mechanism may be related to antioxidant-like action.

Protective Effects of Self-made Compound Taoren Danshen Decoction on Rats with Acute Liver Injury

[Objectives] To study the protective effects of self-made Compound Taoren Danshen Decoction( CTDD) on acute liver injury induced by D-galactosamine in rats,and to explore its mechanism. [Methods]An acute liver injury model was established by intraperitoneal injection of 500 mg/kg of D-galactosamine. The ALT,AST,MDA,SOD and GSH-Px in serum,as well as serum TNF-α,IL-1β and IL-6 levels were measured,and liver tissue lesions were observed under microscope. [Results] CTDD can significantly reduce ALT,AST and MDA levels,increase SOD,GSH-Px activity,and significantly reduce serum TNF-α,IL-1β and IL-6 levels,and improve liver tissue lesions.[Conclusions]CTDD has a protective effect on D-galactosamine-induced acute liver injury in rats,and its mechanism may be related to inhibition of oxidative stress and inflammatory reaction.

Experimental study on EPO treatment of model rats with infection-induced acute liver injury

Objective: To study the effect of EPO therapy on liver injury, inflammation, oxidative stress and cell apoptosis in model rats with infection-induced acute liver injury. Methods: SD rats were selected and randomly divided into Sham group, sepsis group (CLP group) and EPO intervention group (EPO group), the cecal ligation and puncture was adopted to establish sepsis models and 5000IU/kg human recombinant EPO was provided for intervention. 24 hours after intervention, serum levels of liver injury molecules, inflammatory factors and oxidative stress molecules as well as liver tissue levels of oxidative stress molecules and cell apoptosis molecules were detected. Results: Serum ALT, AST, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MDA and AOPP levels, liver tissue Nrf2, ARE, MDA and AOPP levels as well as Bax, Caspase-9 and Caspase-3 mRNA expression of CLP group were significantly higher than those of Sham group while liver tissue HO-1 and SOD levels as well as Bcl-2 mRNA expression were significantly lower than those of Sham group;serum ALT, AST, TNF-α, IFN-γ, IL-1β, IL-6, IL-8, MDA and AOPP levels, liver tissue MDA and AOPP levels as well as Bax, Caspase-9 and Caspase-3 mRNA expression of EPO group were significantly lower than those of CLP group while liver tissue Nrf2, ARE, HO-1 and SOD levels as well as Bcl-2 mRNA expression were significantly higher than those of CLP group. Conclusions: EPO therapy could reduce liver injury and inhibit inflammation, oxidative stress and cell apoptosis in model rats with infection-induced acute liver injury.

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 eff ects 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 eff ects 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.

Protection Effect of Qiwei Jingganling on Carbon Tetrachloride-induced Acute Liver Injury in Mice

[Objectives] The aim was to study the protection effect of Qiwei Jingganling on carbon tetrachloride-induced acute liver injury in mice and its mechanism of action. [Methods]Total 60 mice were randomly and evenly divided into 6 groups,normal group,model group,silymarin group( 150 mg/kg),high-dose Qiwei Jingganling group( 8 g/kg,crude drug),middle-dose Qiwei Jingganling group( 4 g/kg,crude drug) and low-dose Qiwei Jingganling group( 2 g/kg,crude drug). The mice were administered orally once a day according to the amount of10 m L/kg,and 10-day continuous administration was carried out. After 2 h of the last administration,0. 12% CCl4 peanut oil solution( 10 m L/kg) was injected intraperitoneally to all the mice except those in the normal group to establish acute liver injury model. After 16 h,the blood of the mice was collected from the eyeballs,and their liver tissues were collected. The levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),malondialdehyde( MDA) and glutathione peroxidase( GSH-Px) in the sera were determined by biochemical methods,and the contents of tumor necrosis factor-α( TNF-α),interleukin-1β( IL-1β) and interleukin-6( IL-6) in the liver tissues were determined with enzyme-linked immunosorbent assays( ELISA). [Results]Qiwei Jingganling significantly reduced the activities or content of ALT,AST and MDA in serum of mice with liver injury( P < 0. 05,P < 0. 01),increased the activities of SPD and GSH-Px( P < 0. 05,P < 0. 01) and down-regulated the expression levels of IL-1β,IL-6 and TNF-α in liver tissue( P < 0. 05,P < 0. 01).[Conclusions]Qiwei Jingganling has a good protection effect on CCl4-induced acute liver injury in mice,which may be related to the inhibition of oxidative stress and inhibition of inflammatory responses.

Protective Effect and Mechanism of Polysaccharides from Cordyceps cicadae on Acute Liver Injury Induced by D-GlaN in Mice

[Objectives]To observe the protective effect of Cordyceps cicadae polysaccharides on acute liver injury induced by D-galactosamine( D-GlaN) in mice,and to explore its mechanism. [Methods] Seventy-five male Kunming mice were randomly and evenly divided into 5 groups according to the digital table method: normal group( CK)( injected intraperitoneally with saline solution),model group( injected intraperitoneally with D-GlaN),low-dose C. cicadae polysaccharides group( administered with 0. 5 g/kg of C. cicadae polysaccharides solution by gavage),middle-dose C. cicadae polysaccharides group( administered with 1. 0 g/kg of C. cicadae polysaccharides solution by gavage) and high-dose C. cicadae polysaccharides group( administered with 2. 0 g/kg of C. cicadae polysaccharides solution by gavage). After 12 d of administration,the liver histopathological score,liver homogenate indexes( superoxide dismutase,SOD; malondialdehyde,MDA; glutathione peroxidase,GSH-Px; nitric oxide,NO) and serum markers( aspartate transaminase,AST; alanine transaminase,ALT; alkaline phosphatase,ALP; cholinesterase,CHE) of mice in each group were detected. The expression levels of nuclear factor-κB( NF-κB) and tumor necrosis factor-α( TNF-α) in liver tissues were detected by immunohistochemistry. [Results]The liver histopathological score and the MDA,NO,AST,ALT,ALP,NF-κB and TNF-α levels were significantly higher( P < 0. 05) and the SOD,GSH-Px and CHE levels were significantly lower( P <0. 05) in the model group compared with the normal group. Compared with those in the model group,the liver tissue histopathological scores in the low-,middle-and high-dose C. cicadae polysaccharides groups were all significantly reduced( P < 0. 05). With the increase of treatment dose,the liver tissue histopathological scores showed a significant decrease( P < 0. 05). Compared with the model group,the levels of MDA,NO,AST,ALT,ALP,NF-κB and TNF-α were significantly lower( P < 0. 05),and the levels of SOD,GSH-Px and CHE were significantly higher( P < 0. 05) in the low-,middle-and high-dose C. cicadae polysaccharides groups. With the increase of treatment dose,the levels of MDA,NO,AST,ALT,ALP,NF-κB and TNF-α declined significantly( P < 0. 05),while the levels of SOD,GSH-Px and CHE rose significantly( P < 0. 05). [Conclusions] C. cicadae polysaccharides have a significant protective effect on D-GlaN-induced acute liver injury in mice in a dose-dependent manner,and the mechanism may be related to the inhibition of NF-κB inflammatory signaling pathway.

Literature review of the mechanisms of acute kidney injury secondary to acute liver injury

People exposed to liver ischaemia reperfusion(IR)injury often develop acute kidney injury and the combination is associated with significant morbidity and mortality.Molecular mediators released by the liver in response to IR injury are the likely cause of acute kidney injury(AKI)in this setting,but the mediators have not yet been identified.Identifying the mechanism of injury will allow the identification of therapeutic targets which may modulate both liver IR injury and AKI following liver IR injury.

Protective Effects of Flavonoids from Pteridium aquilinum on CCl_(4)-induced Acute Liver Injury in Mice

[Objectives]To explore the protective effects of flavonoids from Pteridium aquilinum(PAFL)on carbon tetracholoride(CCl_(4))-induced acute liver injury in mice and its potential mechanism.[Methods]All mice were randomly divided into four groups(n=10 in each),normal group,CCl_(4)group,CCl_(4)+PAFL groups[treated with PAFL(50 or 200 mg/kg)].Animal treatment was continued for 7 consecutive days.The blood was collected after injection of CCl_(4)for 24 h,and the liver tissue was removed from the mice and stored at-80℃.[Results]The PAFL(50 and 200 mg/kg)significantly inhibited the increase of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in serum caused by CCl_(4)treatment.PAFL administration not only increased the activity of antioxidant enzymes superoxide dismutase(SOD),Glutathione(GSH)and catalase(CAT)in mice,but also reduced the level of malondialdehyde(MDA).Meanwhile,PAFL administration decreased the expression of nuclear factor-kappa B(NF-κB)and Cyclooxygenase-2(COX-2)proteins and inhibited the release of pro-inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin 6(IL-6).In addition,PAFL(200 mg/kg)treatment down-regulated extracellular regulated protein kinases(ERK)and c-Jun N-terminal kinase(JNK)protein levels in liver tissue.[Conclusions]These findings clearly indicate that the protective effects of PAFL on CCl_(4)-induced acute liver injury is related to its antioxidant and anti-inflammatory activity,which may be mediated by NF-κB and MAPKs signaling pathways.