Liver Metabolic Disorders Research Articles

Liver and Metabolic Diseases

Abstract Chronic liver diseases and metabolic disorders represent two real public health problems that cause increased morbidity and mortality in a significant number of people worldwide. The most common cause of chronic liver disease is represented by non-alcoholic fatty liver disease (NAFLD). Hepatic inflammation is a critical event in the progression of NAFLD and excess adiposity, through the hormones and cytokines secreted by the adipose tissue, plays an important role. There is ample evidence supporting a significant association between chronic hepatitis C (CHC) and metabolic disorders. CHC may be considered not just a viral disease, but also a metabolic type condition. Multiple pathogenic mechanisms have been proposed to explain the interaction between hepatitis C virus and impairment of glucose and lipid metabolism and diabetes. The relationship between hepatitis B infection (HBV) and metabolic diseases remains uncertain.

Metabolic disorders in liver in late period of cranial-skeletal trauma and their correction by Thiocetam

<p>In the conditions of cranial-skeletal trauma throughout the period of late signs of traumatic disease (14–28 days),<br />the processes of lipidic peroxidation don’t calm down, the activity of antioxidant protection ferments remains reduced,<br />the pro-oxidant mechanisms dominate. The use of thiocetam in 250 mg/kg dosage intraperatoneal throughout 14<br />days after striking of cranial-skeletal trauma essentially lowers the manifestations of free radical oxidation of the<br />lipids, the activity of superoxide dismutase and catalase increases, the antioxidant mechanisms predominate. By<br />the 28th day the normalization of the most of the indices occurs.</p>

Proteomic Profiling of Histone Posttranslational Modifications in Late Gestation Fetal Hepatocytes Capable of Liver Repopulation

Hepatocyte transplantation has the potential to be an effective therapy for acute liver disease and metabolic disorders. Our laboratory has focused on late gestation (E19) liver development in the rodent. We have identified a fetal hepatocyte phenotype defined by differences in signaling pathways and gene expression. We recently found that E19 hepatocytes expressing the hepatic marker leucine aminopeptidase (LAP) have the ability to repopulate an injured adult liver. Our current studies are based on the hypothesis that histone posttranslational modifications (PTMs) acting through effects on chromatin structure account for the E19 hepatocyte signaling phenotype and the repopulating ability of these cells. We employed a bottom‐up mass spectrometry based approach to profile PTMs on histone H3 and H4 in freshly isolated LAP+ E19 hepatocytes and adult hepatocytes, and cultured adult hepatocytes. In order to mimic the asynchronously proliferating E19 hepatocytes, adult hepatocytes were cultured in the presence of EGF and insulin for time points ranging from 0 to 72 hr and combined into pooled samples for mass spectrometry. We identified significant differences in 10 of the 26 histone PTMs on H3 and H4 comparing the asynchronously proliferating LAP+ E19 and cultured adult hepatocytes. In summary, late gestation fetal hepatocytes capable of liver repopulation possess a histone PTM profile that is distinct from that of adult hepatocytes.

Deficiency of Capicua disrupts bile acid homeostasis.

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type 1 and cancer in mammals; however, the in vivo physiological functions of CIC remain largely unknown. Here we show that Cic hypomorphic (Cic-L-/-) mice have impaired bile acid (BA) homeostasis associated with induction of proinflammatory cytokines. We discovered that several drug metabolism and BA transporter genes were down-regulated in Cic-L-/- liver, and that BA was increased in the liver and serum whereas bile was decreased within the gallbladder of Cic-L-/- mice. We also found that levels of proinflammatory cytokine genes were up-regulated in Cic-L-/- liver. Consistent with this finding, levels of hepatic transcriptional regulators, such as hepatic nuclear factor 1 alpha (HNF1α), CCAAT/enhancer-binding protein beta (C/EBPβ), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXRα), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (Tnfα) expression and decrease in the levels of FOXA2, C/EBPβ, and RXRα were found in Cic-L-/- liver before BA was accumulated, suggesting that inflammation might be the cause for the cholestasis in Cic-L-/- mice. Our findings indicate that CIC is a critical regulator of BA homeostasis, and that its dysfunction might be associated with chronic liver disease and metabolic disorders.

Puerarin ameliorates hepatic steatosis by activating the PPARα and AMPK signaling pathways in hepatocytes.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the hepatic manifestation of metabolic syndrome and is the leading cause of chronic liver disease. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Puerarin is a herbal product widely used in Asia, and is believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. The present study was designed to investigate the effects and mechanisms of action of puerarin in reducing lipid accumulation in oleic acid (OA)-treated HepG2 cells. Hepatocytes were treated with OA with or without puerarin to observe lipid accumulation by Oil Red O staining. We also examined hepatic lipid contents (e.g., triacylglycerol and cholesterol) following treatment with puerarin. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), peroxisome proliferator-activated receptor α (PPARα) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) protein and mRNA expression, respectively. Our results revealed that puerarin suppressed OA-induced lipid accumulation, and reduced the triacylglycerol and cholesterol levels. Furthermore, puerarin decreased the expression levels of lipogenic enzymes, such as FAS and SREBPs, and increased the expression levels of PPARα, which are critical regulators of hepatic lipid metabolism through the AMPK signaling pathway. These results indicate that puerarin has the same ability to activate AMPK, and reduce SREBP-1 and FAS expression, thus inhibiting hepatic lipogenesis and increasing hepatic antioxidant activity. We found that puerarin exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in hepatocytes. Therefore, puerarin extract may have therapeutic benefits in the treatment of fatty liver and lipid-related metabolic disorders.

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs.FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, the animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopathy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of the efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes.

Metabolic disorders of liver and iron in diabetic and non-diabetic patients BMI < 35 or > 35 before gastric bypass.

The presence of abnormalities in the metabolic pathways of iron and liver functioning can produce insulin resistance or metabolic syndrome. Therefore, it is important to examine those alterations that may lead to the development of diseases. Nutritional status is another important factor that is intimately linked to diabetes and obesity. We studied 131 patients (78 nondiabetic patients and 53 diabetic), 37 patients BMI ≤35 (3 BMI < 25, 18 BMI 25-29.9, 16 BMI 30-34.9) and 94 patients BMI ≥35 (81 BMI 35-49.9 and 13 BMI ≥50). Subjects underwent to laboratory studies related to liver functioning and iron metabolism. Nutritional status was also determined in our patients. Iron was altered 14% of patients BMI >35 and diabetics reached 3% to 25%. Vitamin B12 was low 4% of non-diabetics BMI > 35, and high in 6% of diabetics BMI < 35. The 6% of diabetics BMI < 35 had hyperbilirubinemia. Transaminases are elevated in patients BMI >35 but exacerbated on diabetics. GGT is raised 41% to 47% in BMI >35. ALP is elevated in 25% of diabetics. Total protein and serum albumin were altered in diabetics causing mild malnutrition. 90% of patients had normal nutrition and 10% mild malnutrition. The metabolisms Hepatic and iron are closely related to the onset of obesity and diabetes. If there is weight gain, cumulative metabolic risks rise. The presence of diabesity and increased duration of diabetes produce altered metabolism. Nutritional status is altered in obesity but is worse with the addition of diabetes.

Alteration of protein profile in rat liver of animals exposed to subacute diazinon: A proteomic approach

Diazinon, an organophosphorus insecticide, is employed to control pests in agriculture. Diazinon may contaminate the environment during the manufacturing process or agricultural application. Previous studies have revealed that diazinon may induce alteration in the protein profile of the liver. Here, a proteomics approach was used to investigate the effects on the protein profile in the liver of rats of subacute oral exposures at 15 mg/kg of diazinon. Liver proteins were separated using 2D-PAGE, and stained by MS-compatible silver staining and/or the fluorescent SYPRO® Ruby protein gel stain. Gels were scanned and analyzed using the Image Master software. Differentially displayed protein species were identified using MALDI-TOF/TOF and MASCOT software. Significantly altered protein species were identified to be involved in apoptosis, cell metabolism, transport, and antioxidant systems. Exposure to diazinon decreased levels of some species of catalase, peroxiredoxin-6, 3-ketoacyl-CoA thiolase, and glucose regulated protein78, whereas the level of protein disulfide-isomerase A3 increased. Our results suggested that diazinon may induce hepatotoxicity through oxidative stress, apoptosis, and metabolic disorders in rat liver.

MicroRNAs: the fine modulators of liver development and function

MicroRNAs are a class of small non-coding RNAs involved in the transcriptional and post-transcriptional regulation of gene expression. The function of miRNAs in liver disease including hepatocellular carcinoma (HCC), hepatitis, and alcoholic liver disease, have been widely studied and extensively reviewed. Increasing evidence demonstrates that miRNAs also play a critical role in normal liver development and in the fine-tuning of fundamental biological liver processes. In this review, we highlight the most recent findings on the role of miRNAs in liver specification and differentiation, liver cell development, as well as in the many metabolic functions of the liver, including glucose, lipid, iron and drug metabolism. These findings demonstrate an important role of miRNAs in normal liver development and function. Further researches will be needed to fully understand how miRNAs regulate liver generation and metabolic function, which should then lead to greater insights in liver biology and perhaps open up the possibility to correct errors that cause liver diseases or metabolic disorders.

Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India.

Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding "common mutations" in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much delay in diagnosis with consequent harm to the patient.We report mutations in the ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal community. Six patients from the Agarwal community and two non-Agarwal patients harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous), in the ALDOB gene. Haplotyping performed in families confirmed a founder effect. The community has been known to harbor founder mutations in other genes such as the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder effect in the community in case of HFI. This may pave the path for a simpler and quicker test at least for this community in India. In addition to the founder mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A, c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the cohort from India.

Perinatal liver pathology

The pathologist may encounter perinatal liver disease at autopsy, when examining a stillbirth or neonatal death, or on liver biopsy to investigate the cause of neonatal jaundice or liver failure. This presentation aims to discuss the pathology of liver disease of intrauterine or neonatal onset. A pattern based approach is used. Even when a specific diagnosis is not reached, identification of the pattern of liver injury, in conjunction with clinical and laboratory findings often narrows the differential diagnosis and thereby assists in further decision making. Neonatal liver disease most commonly manifests with cholestatic jaundice/conjugated hyperbilirubinemia. Other presentations include neonatal liver failure, fetal hydrops, IUGR and stillbirth. Neonatal jaundice may be idiopathic, due to infection (viral, bacterial), metabolic or endocrine disorders, or toxic/drug related. The main causes of perinatal liver failure are neonatal hemochromatosis, inherited metabolic disorders and viral infections. In neonatal hemochromatosis the liver typically shows signs of subacute or chronic liver injury. Hepatic necrosis is characteristically seen in neonatal viral infections, or drug induced liver injury and metabolic disorders. Steatosis, cholestatic resetting and storage cells strongly suggest an underlying metabolic disorder. Use of special stains or electronmicroscopy in many cases will allow identification of storage material.

Liver resection and metabolic disorders: an undescribed mechanism leading to postoperative mortality.

To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders. The link between Metabolic Syndrome and non-alcoholic fatty liver disease is currently demonstrated. Various metabolic disorders and the Metabolic Syndrome (the association of ≥ 3 metabolic disorders) have been recently described as a risk factor of perioperative mortality in major liver resection. Patients who passed away during perioperative course of major liver resection and presenting with the association of ≥ 2 metabolic disorders without any other known cause of liver disorders were reviewed. From January 2001 to May 2010 in a tertiary centre, ten patients presenting with ≥ 2 metabolic disorders without any other known cause of liver disorders died during perioperative course of major liver resection. The same four-consecutive-steps sequence of events occurred, including jaundice. The analysis of this series suggested a rapidly deteriorating congestive liver resulting in an increased portal hypertension leading to hepatorenal syndrome and lately to multiorgan failure (mimicking septic collapse) as the mechanism leading to exitus. The acute portal hypertension is mainly related to the surgical procedure. The chronic portal hypertension is indeterminate. Patients with ≥ 2 metabolic disorders should be considered as potentially presenting with portal hypertension possibly evolving towards hepatorenal syndrome; thus, they should be considered as having a high perioperative risk and should be carefully evaluated before undergoing major liver resection. As fibrosis was not present or marginal in liver specimens, the real cause of portal hypertension in patients with multiple metabolic disorders should be investigated with further studies.

Efficient Generation of Hepatic Cells from Multipotent Adult Mouse Germ-Line Stem Cells Using an OP9 Co-Culture System

On the basis of their self-renewal capacity and their ability to differentiate into derivatives of all three germ layers, germ line-derived multipotent adult stem cells (maGSCs) from mouse testis might serve as one of preferable sources for pluripotent stem cells in regenerative medicine. In our study, we aimed for an efficient hepatic differentiation protocol that is applicable for both maGSCs and embryonic stem cells (ESCs). We attempted to accomplish this goal by using a new established co-culture system with OP9 stroma cells for direct differentiation of maGSCs and ESCs into hepatic cells. We found that the hepatic differentiation of maGSCs was induced by the OP9 co-culture system in comparison to the gelatin culture. Furthermore, we showed that the combination of OP9 co-culture with activin A resulted in the increased expression of endodermal and early hepatic markers Gata4, Sox17, Foxa2, Hnf4, Afp, and Ttr compared to differentiated cells on gelatin or on OP9 alone. Moreover, the hepatic progenitors were capable of differentiating further into mature hepatic cells, demonstrated by the expression of liver-specific markers Aat, Alb, Tdo2, Krt18, Krt8, Krt19, Cps1, Sek, Cyp7a1, Otc, and Pah. A high percentage of maGSC-derived hepatic progenitors (51% AFP- and 61% DLK1-positive) and mature hepatic-like cells (26% ALB-positive) were achieved using this OP9 co-culture system. These generated hepatic cells successfully demonstrated in vitro functions associated with mature hepatocytes, including albumin and urea secretion, glycogen storage, and uptake of low-density lipoprotein. The established co-culture system for maGSCs into functional hepatic cells might serve as a suitable model to delineate the differentiation process for the generation of high numbers of mature hepatocytes in humans without genetic manipulations and make germ line-derived stem cells a potential autologous and alternative cell source for hepatic transplants in metabolic liver disorders.

A Report from the 2013 International Workshop: Radiation and Cardiovascular Disease, Hiroshima, Japan

Two longitudinal cohort studies of Japanese atomic bomb survivors—the life span study (LSS) and the adult health study (AHS)—from the Radiation Effects Research Foundation (RERF) indicate that total body irradiation doses less than 1 Gy are associated with an increased risk of cardiovascular disease (CVD), but several questions about this association remain. In particular, the diversity of heart disease subtypes and the high prevalence of other risk factors complicate the estimates of radiation effects. Subtype-specific analyses with more reliable diagnostic criteria and measurement techniques are needed. The radiation effects on CVD risk are probably tissue-reaction (deterministic) effects, so the dose–response relationships for various subtypes of CVD may be nonlinear and therefore should be explored with several types of statistical models. Subpopulations at high risk need to be identified because effects at lower radiation doses may occur primarily in these susceptible subpopulations. Whether other CVD risk factors modify radiation effects also needs to be determined. Finally, background rates for various subtypes of CVD have historically differed substantially between Japanese and Western populations, so the generalisability to other populations needs to be examined. Cardiovascular disease mechanisms and manifestations may differ between high-dose local irradiation and low-dose total body irradiation (TBI)—microvascular damage and altered metabolism from low-dose TBI, but coronary artery atherosclerosis and thrombotic myocardial infarcts at high localised doses. For TBI, doses to organs other than the heart may be important in pathogenesis of CVD, so data on renal and liver disorders, plaque instability, microvascular damage, metabolic disorders, hypertension and various CVD biomarkers and risk factors are needed. Epidemiological, clinical and experimental studies at doses of less than 1 Gy are necessary to clarify the effects of radiation on CVD risk.

Cumulative Amount of Intravenous Lipid Intake and Parenteral Nutrition-Associated Cholestasis in Neonates with Gastrointestinal Surgical Disorders

To evaluate if cumulative amount of intravenous lipid (IL) intake is associated with severity of parenteral nutrition (PN)-associated cholestasis (PNAC) in neonates with gastrointestinal surgical disorders (GISD). The authors performed a retrospective study including 36 neonates > 34 weeks gestational age with GISD. Neonates with metabolic liver disorders, chromosomal disorders, TORCH infections, which includes toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes, biliary tract anomalies, or direct hyperbilirubinemia (DHB) within first postnatal week were excluded. There was no significant difference in clinical factors between three groups of neonates: (1) without PNAC (n = 13), (2) with mild-to-moderate PNAC (DHB 1-5 mg/dL, n = 12), and (3) with severe PNAC (DHB > 5 mg/dL or PNAC with elevated amino-transaminases, n = 11) except for duration of enteral starvation and PN. Using ordered logistic regression, cumulative amount of IL, glucose, and protein intake were independently associated with severity of PNAC (p < 0.05). Comparing macronutrients as predictors of severe PNAC using receiver operating characteristic curves, the area under the curve for IL (0.583) intake was significantly larger (p = 0.008) compared with intravenous protein (0.257) and glucose (0.431) intake. IL intake is associated with and is a better predictor of severity of PNAC in neonates with GISD.

Progress of the liver transplantation programme in Hungary

The history of organ transplantation in Hungary dates back to 50 years, and the first succesful liver transplantation was performed in the United States in that time as well. The number of patients with end stage liver disease increased worldwide, and over 7000 patients die in each year due to liver disease in Hungary. The most effective treatment of end-stage liver disease is liver transplantation. The indications of liver transplantation represent a wide spectrum including viral, alcoholic or other parenchymal liver cirrhosis, but cholestatic liver disease and acute fulminant cases are also present in the daily routine. In pediatric patients biliary atresia and different forms of metabolic liver disorders represent the main indication for liver transplantation. The results of liver transplantation in Hungary are optimal with over 80% long-term survival. For better survival individual drug therapy and monitoring are introduced in liver transplant candidates.

Improved Hepatic Differentiation Strategies for Human Induced Pluripotent Stem Cells

Based on their almost unlimited self-renewal capacity and their ability to differentiate into derivatives of all three germ layers, human induced pluripotent stem cells (hiPSCs) might serve as a preferable source for hepatic transplants in metabolic liver disorders or acute liver failure. Furthermore, the generation of patient specific hiPSCs might facilitate the development of innovative therapeutic strategies by accurately modelling disease in vitro. In our study, we aimed for an efficient hepatic differentiation protocol that is applicable for both human embryonic stem cells (hESCs) and hiPSCs. We attempted to accomplish this goal by using a cytokine and small molecule-based protocol for direct differentiation of hESCs and hiPSCs into hepatic cells. Selecting differentiated hepatic cells was possible using an albumin promoter-driven G418 resistance system. Due to IRES-dependent dTomato reporter expression, we were able to track hepatic differentiated cells and we evaluated the most efficient time frame for G418 selection. The status of hepatic differentiation was determined by qRT-PCR comparing the expression of hepatic markers such as AFP, ALB, SOX17, and HNF4 to standard hepatic cells. Functional analysis of the hepatic phenotype was obtained by measuring secreted albumin levels and by analysis of cytochrome P450 type 1A1 activity (EROD). The percentage of differentiated cells was quantified by FACS analysis. In conclusion, our improved protocol demonstrates that both pluripotent cell sources (hESC and hiPSC) can efficiently be differentiated into mature hepatic cells with functional characteristics similar to those of standard hepatic cell lines such as HepG2.

Retransplantation of the Liver: Review of Current Literature for Decision Making and Technical Considerations

Liver transplantation (LTx) is an established treatment modality for patients with end-stage liver disease, metabolic disorders, and patients with acute liver failure. When a graft fails after primary LTx, retransplantation of the liver (reLTx) is the only potential cure. ReLTx accounts for 7%–10% of all LTx in the United States. Early causes of graft failure for which reLTx may be indicated include primary graft nonfunction and vascular inflow thrombosis. ReLTx in such cases in the early postoperative period is usually straightforward as long as an appropriate secondary allograft is secured in a timely fashion. Late indications may include ischemic cholangiopathy, chronic rejection, and recurrence of the primary liver disease. ReLTx performed in the late period is often more complex and selection criteria are more stringent due to the persistent shortage of organs. The question of whether to retransplant patients with recurrent hepatitis C remains controversial, but these practices are likely to change as the epidemic progresses and new treatments evolve. We also present recent results with reLTx from Yale–New Haven Transplant Center and early results with the use of living donors for reLTx.

Noninvasive monitoring of liver cell transplantation

Liver cell transplantation was developed as a therapeutic alternative to solid liver transplantation in the management of liver-based metabolic disorders and may be useful for the treatment of acute or chronic liver failure. While clinical studies have demonstrated temporal amelioration of the symptoms of metabolic liver disorders by transplanted liver cells, the long-term outcome of liver cell transplantation is still insufficient. A major limitation for improving liver cell transplantation is the inability to track the fate of cells once they have been infused. Radionuclide-based imaging, MRI and optical methods have been investigated as methods for noninvasive monitoring of liver cell transplantation. This article summarizes and critically discusses these approaches, with a special focus on MRI-based tracking of transplanted liver cells and provides an outlook on possible clinical applications for the near future.

Gene expression profile in chronic mouse liver injury caused by long‐term exposure to CeCl3

Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and the corresponding damage; however, very little work has been done to evaluate the relationship between Ln-induced liver injury and its gene expression profile in mice. In this study, liver injury and gene-expressed profiles in male mice induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive days were investigated. The results showed that cerium accumulation, liver inflammation, and hepatocyte necrosis were observed. CeCl3 exposure significantly decreased the counts of white blood cells, lymphocyte, and platelet, the reticulocyte count (Ret) and neutrophilic granulocyte percentages as well as A/G ratio, whereas markedly increased the activities of alkaline phosphatase, lactate dehydrogenase, and cholinesterase, and the concentrations of triglycerides and total cholesterol. Furthermore, microarray results of liver showed that the differential expression of 675 known function genes involved in immune/inflammation response, apoptosis, metabolic process, cell cycle, cell proliferation, cytoskeleton, oxidative stress, signal transduction, transcription, translation, and transportation in CeCl3 exposed livers, respectively. Specifically, the significant downregulation of Nt5e led to inflammation, overexpressed Cyp4a12a and great suppression of Cdkn1a resulted in hepatocyte apoptosis, marked elevation of Cel, and Cyp7b1 expression caused the metabolic disorders in mouse liver after long-term CeCl3 exposure. Therefore, these genes may be in great relation to liver damages induced by exposure to CeCl3 .