Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation(LT)provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma.Despite the increasing number of liver transplants performed each year,the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality.Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates.Nevertheless,further strategies can be implemented to increase the pool of potential donors in deceased donor LT,such as reducing the rate of organ discards.Utilizing hepatitis C virus(HCV)seropositive liver grafts is one of the expanded donor organ criteria.A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients.Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation.The American Society of Transplantation advises against performing transplants from HCV-infected liver donors(D+)into HCV-negative recipient(R-)unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants.Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is im-portant.National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Expression of P450 and nuclear receptors in normal and end-stage Chinese livers

AIM: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers.

Detection and characterization of Hepatitis E virus from commercial rabbit livers in Hebei, China

Rabbit hepatitis E virus(HEV)has been reported for years and is thought to have the potential for zoonotic transmission from rabbits to humans.As reported,HEV genotype 3(gt3)is the most prevalent form of HEV in rabbits.To determine the prevalence of HEV in commercial rabbit livers,176 liver samples were collected from an abattoir in Hebei Province,China.Three(1.7%)samples tested positive for RNA of HEV-0RF2(open reading frames-2).Sequence analysis showed that the three isolates shared high identities with each other(94.08-98.85%).Further analysis showed that all the rabbit strains clustered together in the branch of HEV gt3.Further study by immunohistochemistry(IHC)assays showed that 131(74.4%)liver samples were positive for HEV ORF2 protein.Pathological changes including cell degeneration,inflammatory cell infiltration and bile duct epithelial cell hyperplasia were observed under microscopy.These findings indicated the presence of HEV in commercial livers of rabbits.Additional studies should be conducted to investigate the infectivity of rabbit HEV(rHEV)and the potential risks of zoonotic transmission of rHEV from rabbits to human beings.

THE ACTIVITY OF 0~6-METHYLGUANINE DNA METHYL-TRANSFERASE IN LIVERS OF DUCKS FROM QIDONG AND QINGPU

O6-methylguanine DNA methyltransferase (O6-AT) is an enzyme for the repair of the promutagenic structure, O6-aIkylguanine, from alkylated DNA, therefore low activity of O6-AT is involved in the predisposition of tissues to some nitrosamines and the development of cancer. The levels of O6-AT in livers of ducks from Qidong (Qd), a high incidence area of liver cancer, and from Qingpu(Qp), a relatively low incidence area were determined in this study. The results showed that the activity of O6-AT was higher in Qp than in Qd. It suggested that some nitrosamine in Qd might be one of factors responsible for the higher incidence of ducks liver cancer, because these ducks were more sensitive to nitrosa-mine.

“Liverscore”is predictive of both liver fi brosis and activity in chronic hepatitis C

AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis C.METHODS:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave patients.Fibrosis was staged on a f ive point scale from F0-F4 and activity was graded on a four point scale from A0-A3,according to the METAVIR system.Patients were divided into two overall severity groups,minimal disease(< F2 and < A2)and signif icant disease(≥ F2 or ≥ A2).Eleven markers were measured in blood.Sta-tistically,the primary outcome variable was identif ica-tion of minimal and signif icant overall disease.Indices were formulated using β regression values of different combinations of nine statistically significant factors.Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis.RESULTS:A total of 98 patients were included and of these 46 had an overall clinically significant disease.Our f inal six marker index,Liverscore for Hepatitis C,consisted of age,alanine transaminase,gamma-gluta-myl transpeptidase,apolipoprotein A-1,alpha-2 macro-globulin and hyaluronic acid.The area under the curve was found to be 0.813.On a 0-1 scale,negative predic-tive value at a cutoff level of ≤ 0.40 was 83%,while positive predictive value at ≥ 0.80 remained 89%.Al-together,61% of the patients had these discriminative scores.CONCLUSION:This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical de-cision making.

Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury:The role of Kupffer cells

AIM:To examine whether heme oxygenase (HO)-1 overexpression would exert direct or indirect effects on Kupffer cells activation, which lead to aggravation of reperfusion injury.METHODS: Donors were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4℃ for 24 h before transplantation. Kupffer cells were isolated and cultured for 6 h after liver reperfusion.RESULTS: Postoperatively, serum transaminases were significantly lower and associated with less liver injury when donors were pretreated with CoPP, as compared with the ZnPP group. Production of the cytokines tumor necrosis factor-α and interleukin-6 generated by Kupffer cells decreased in the CoPP group. The CD14 expression levels (RT-PCR/Western blots) of Kupffer cells from CoPP-pretreated liver grafts reduced.CONCLUSION: The study suggests that the potential utility of HO-1 overexpression in preventing ischemia/reperfusion injury results from inhibition of Kupffer cells activation.

Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.

Progress in bioreactors of bioartificial livers

BACKGROUND: Bioartificial liver support systems are becoming an effective therapy for hepatic failure. Bioreactors, as key devices in these systems, can provide a favorable growth and metabolic environment, mass exchange, and immunological isolation as a platform. Currently, stagnancy in bioreactor research is the main factor restricting the development of bioartificial liver support systems. DATA SOURCES: A PubMed database search of English-language literature was performed to identify relevant articles using the keywords 'bioreactor', 'bioartificial liver', 'hepatocyte', and 'liver failure'. More than 40 articles related to the bioreactors of bioartificial livers were reviewed. RESULTS: Some progress has been made in the improvement of structures, functions, and modified macromolecular materials related to bioreactors in recent years. The current data on the improvement of bioreactor configurations for bioartificial livers or on the potential of the use of certain scaffold materials in bioreactors, combined with the clinical efficacy and safety evaluation of cultured hepatocytes in vitro, indicate that the AMC (Academic Medical Center) BAL bioreactor and MELS (modular extracorporeal liver support) BAL bioreactor system can partly replace the synthetic and metabolic functions of the liver in phase I clinical studies. In addition, it has been indicated that the microfluidic PDMS (polydimethylsiloxane) bioreactor, or SlideBioreactor, and the microfabricated grooved bioreactor are appropriate for hepatocyte culture, which is also promising for bioartificial livers. Similarly, modified scaffolds can promote the adhesion, growth, and function of hepatocytes, and provide reliable materials for bioreactors. CONCLUSIONS: Bioreactors, as key devices in bioartificial livers, play an important role in the therapy for liver failure both now and in the future. Bioreactor configurations are indispensable for the development of bioartificial livers used for liver failure, just as the modified scaffold materials available for bioreactors are favorable to the construction of effective bioartificial livers.

Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

AIM： To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions （IITBLs）. METHODS： A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS： In the control group, the incidence of IITBLs was 5.9% （13/220 cases） after 3-11 mo of transplantation. In the experimental group, two recipients （1.4%） developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant （P 〈 0.05）. CONCLUSION： Double from non-heart-beating perfusion of cadaveric livers donors with urokinase may reduce the incidence of IITBLs.

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis

AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Isolation, characterization and culture of Thy1-positive cells from fetal rat livers

AIM： To investigate whether Thyl recognizes oval cells in the fetal liver and to characterize the cultured Thy1 selected cells from E14 rat livers. METHODS： Thyl populations were analyzed by fluorescence activated cell sorter analysis. Thyl positive cells were isolated using magnetic beads. Hepatic markers were detected by Western blotting, immunocytochemistry and RT-PCR. RESULTS： The percentage of Thyl-positive cells decreased during early development of fetal rat liver （E13-E16）. E14 fetal livers contained 7.8% Thy1 positive cells, of which 61% were positive for α-fetoprotein （AFP） and 25% expressed albumin. The Thy1＋ population expressed oval cell markers c-Kit and CXCR4, liver enriched-transcription factors HNF1α and HNF6, hepatocytic markers albumin, AFP and cytokeratin 18, and biliary marker cytokeratin 19. Thy1- selected cells formed only mesenchymal colonies when plated on collagen and in serum-containing media. Thyl selected cells were able to form hepatic colonies positive for HNF1α, HNF6, albumin, AFP, cytokeratin 18, cytokeratin 19 and glycogen, when grown on STO feeder layers in serum free-media. CONCLUSION： Oval cells positive for Thyl are present in early liver embryonic stages.

Preservation of non-heart-beating donor livers in extracorporeal liver perfusion and histidine-trytophan-ketoglutarate solution

AIM: To compare the preservation of non-heart- beating donor (NHBD) livers in cold histidine-trytophan- ketoglutarate (HTK) solution and extracorporeal liver perfusion (ECLP). METHODS: Livers harvested from health pigs were stored for 10 h in cold HTK solution (group A, n = 4) or perfused with oxygenated autologous blood at body temperature (group B, n = 4). Both groups were then tested on the circuit for 4 h. Bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of extracorporeal livers were tested in each group. Liver tissues from each group were examined at the end of reperfusion. RESULTS: At 1, 2, 3 and 4 h after reperfusion, bile production, hemodynamic parameters, hepatocyte markers and reperfusion injury of livers in group A were statistically different from those in group B (P < 0.05 or P < 0.01). CONCLUSION: ECLP is better than HTK solution to preserve NHBD livers. ECLP can assess the graft viabilitybefore liver transplantation.

The effects of ischemia-reperfusion injury and hepatic artery ischemia on CD14 expression in canine auto-transplantation livers

Objective： To study the effect of ischemia-reperfusion injury（IRI） and hepatic artery ischemia（HAI） on CD14 expression in canine auto-transplantation livers. Methods：Liver orthotopic auto-transplantation models were applied with 30 healthy male Xi＇ an canines which were randomly divided into a control group, simultaneous reperfusion（SR） group and HAI group, CD14 protein expression, Malonaldehyde （MDA） Contents in hepatic tissues and ALT values in serum were detected, and the pathological changes of hepatic tissues was investigated under the light microscopy. Results：The level of CD14 protein expression in SR and HAI group tended to be time-dependent and both higher than controls with statistical significance（P 〈 0.01）; The peak values of these two groups both occurred at 4 h, but the level in HAI group （11.94 ± 0.43） was evidently higher than that in SR group（3.04 ± 0.34）. MDA contents in liver tissue, ALT values in serum and pathological changes showed the same changing tendency as CD 14 expression. Conclusion：（1） Up-regulation of CD14 expression may be the receptor-mechanism of Kupffer cells（KCs） activation in liver transplantation. （2） HAI can upregulate CD14 expression after portal vein reperfusion, improve the activity of KCs further more, increase OFRs production and cooperate with portal reperfusion, and finally aggravate the grafts injury.

Effect of ginkgo biloba extract on livers in aged rats

AIM: To investigate the protective effect of ginkgo biloba extract (GBE) on livers of aged rats and the associated mechanisms.METHODS: Two-mo- and 20-mo-old rats were treated with GBE/saline for 3 mo. Liver tissue samples from 5-moold rats treated with saline (group Y) and 23-mo-old rats treated with GBE (group E) or saline (group N) were used for histopathological examinations (hematoxylin-eosin and Masson staining, Lipofuscin staining-Schmorl staining) and determination of expression of tissue inhibitor-1 of metalloproteinase (TIMP-1) and the level of malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Blood samples were collected for determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and albumin.RESULTS: Microscopic studies with Masson staining revealed mild liver fibrosis in aged rats (group N), while the livers of aged rats receiving GBE (group E) showed amelioration in fibrosis (2.2±0.1 vs 2.8±0.1, P＜0.01) and deposition of lipofuscin (33.7±5.3 vs 62.8±5.7, P＜0.01).The expression of TIMP-1 and the level of liver MDA (1.0±0.1 vs 1.2±0.2, P＜0.05) also decreased but the activity of GPx (97.1±15.3 vs 61.8±14.5, P＜0.01) increased in group E. Compared with group Y, the level of liver MDA (0.8±0.1 vs 1.2±0.2, P＜0.01), lipofuscin (32.4±6.0 vs 62.8±5.7, P＜0.01) and TIMP-1 expression were increased,while the activity of GPx (103.2±17.6 vs61.8±14.5, P＜0.01)and SOD (16.7±4.4 vs 11.8±3.9, P＜0.05) was decreased in group N. There was no difference in liver function among these three groups.CONCLUSION: GBE has protective effects on aging liver.The possible mechanisms might be its antioxidant activity and inhibition of TIMP-1 expression.

Steatotic livers are susceptible to normothermic ischemiareperfusion injury from mitochondrial Complex-Ⅰ?dysfunction

AIM: To assess the effects of ischemic preconditioning(IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury(IRI).METHODS: Sixty male Sprague-Dawley rats were fed8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups(n = 10/group) for each dietary state were tested:(1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion;(2) the IPC group underwent IPC prior to same standard IRI; and(3) sham underwent t h e s a m e s u r g e r y w i t h o u t I R I o r I P C. H e p a t i c mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-Ⅰ, Complex-Ⅱ enzyme activity, serum alanine aminotransferase(ALT), and histological injury were measured.RESULTS: Steatotic-IRI livers had a greater increase in ALT(2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-Ⅰ?activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-Ⅰ?function post-IRI compared to the lean liver IRI group. Complex-Ⅱ activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-Ⅰ?activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

Strategies to rescue steatotic livers before transplantation in clinical and experimental studies

The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications posttransplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g. , peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g. , tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.

Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

AIM： To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS： Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS： After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy （10%） had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION： The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P < 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

Bioengineered functional humanized livers： An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases

End stage liver diseases （ESLD） represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.

Effects of Exposure to Lead and Cadmium on the Oxidative Damage of Livers in Laying Hens

[Objective] To detect the effects of exposure to lead and cadmium on the oxidative damage of livers in laying hens. [Methods] One hundred and twenty 40-week-old Hyline brown hens were randomly divided into four groups. 100 mg / L Pb and / or 50 mg / L Cd was added into the drinking water for eight weeks. [Results] Compared with control group,AST and ALT activities in Pb group enhanced; but there were no significant differences. AST and ALT activities in Cd group and( Pb + Cd) group significantly or extremely significantly increased( P 【 0. 05 or P 【 0. 01). SOD activity,GSH- Px activity and GSH content in( Pb + Cd) group,Cd group and Pb group were significantly or extremely significantly lower than those in control group( P 【0. 05 or P 【0. 01). Among them,( Pb + Cd) group showed the greatest reduction( P 【0. 01). MDA contents in the three groups were significantly higher than that of control group; and( Pb +Cd) group was significantly higher than Pb group and Cd group. Cu,Fe and Zn contents in three groups were higher than those in control group in different degrees( P 【0. 05 or P 【0. 01). Se contents in Cd group and( Pb + Cd) group were significantly lower than that in control group( P 【0. 01). Residue contents in livers in Pb group and Cd group were significantly greater than that in control group; while residue content in( Pb + Cd) group was significantly higher than those in Pb group and Cd group. Ultrastructure showed that there were symptoms of mitochondrial swelling and fractured cristae in liver cells of laying hens after the exposure to Cd and Pb. In( Pb + Cd) group,these symptoms were even greater. [Conclusion] Oxidative damage and disturbance of trace element metabolism were one of the mechanisms for hepatotocity in laying hens induced by Pb and Cd,and synergistic effect lied in the coadministration.