Galactosamine-induced Liver Injury Research Articles

Abstract 1441 Resolvin-D1 treatment ameliorated ethanol and galactosamine-induced liver injury and inflammation in an experimental model of alcohol-associated hepatitis

Abstract 1441 Resolvin-D1 treatment ameliorated ethanol and galactosamine-induced liver injury and inflammation in an experimental model of alcohol-associated hepatitis

Biological Effects of Korean Red Ginseng Polysaccharides in Aged Rat Using Global Proteomic Approach.

Much has been written on the physiological benefits of Korean Red Ginseng (KRG). Among its various components, ginsenosides have been widely investigated for their various pharmacological effects. However, polysaccharides are a major KRG component that has not received scrutiny similar to that of ginsenosides. The present study aims to fill that gap in the existing literature and to investigate the possible functions of polysaccharide in KRG. The researchers evaluated proteomic changes in non-saponin fractions with rich polysaccharides (NFP) in KRG. Based on the serum analysis, proteomics analysis of the liver and the spleen was additionally conducted to identify related functions. We validated the suggested functions of NFP with the galactosamine-induced liver injury model and the cyclophosphamide-induced immunosuppression model. Then, we evaluated the antimetastatic potential of NFP in the lungs. Further proteomics analysis of the spleen and liver after ingestion confirmed functions related to immunity, cancer, hepatoprotection, and others. Then, we validated the suggested corresponding functions of the NFP in vivo model. NFP showed immune-enhancing effects, inhibited melanoma cell metastasis in the lung, and decreased liver damage. The results show that using the proteomic approach uncovers the potential effects of polysaccharides in KRG, which include enhancing the immune system and protecting the liver.

Protective effect of sulfated polysaccharide isolated fromUlva fasciataagainst galactosamine-induced liver injury in rats

The hepatoprotective potential of sulfated polysaccharide (SPS) from Ulva fasciata seaweed against galactosamine (GalN)-induced hepatotoxicity was investigated. Subcutaneous injection of 300 mg/kg GalN into rats caused acute liver injury as manifested by the downregulation of sirtuin 1 (SIRT1) gene expression and induction of hepatic proinflammatory cytokines production, and fibrosis as demonstrated by the significant upregulation of hepatic transforming growth factor beta 1 (TGF-β1) and collagen type I (Col1a1) genes expression. Conversely, pretreatment of rats with SPS attenuated GalN-induced hepatotoxicity via inducing liver SIRT1 gene expression and suppressing proinflammatory cytokines synthesis, which ultimately reduced liver fibrogenesis. Histological findings of liver tissues verified the biochemical data. The study clarified some of the molecular mechanisms by which SPS isolated from U. fasciata protects the liver against acute GalN-induced injury. Practical applications The results suggest the potential use of this edible SPS isolated from Ulva fasciata as a food additive to prevent and/or attenuate development of hepatitis.

Effect of globin digest on the liver injury and hepatic gene expression profile in galactosamine-induced liver injury in SD rats

Aims We investigated the effect of globin digest (GD) on the liver injury and hepatic gene expression profile in galactosamine (GalN)-induced liver injury. Main methods The effect of GD on the liver injury was examined by measuring the activities of serum transferases and hepatic antioxidant enzymes, histopathological analysis, gene expression profile, and proteins of the peroxisome proliferator-activated receptor alpha (PPARα) and met proto-oncogene (c-Met) in SD rats at 24 h after GalN administration. The effect of GD on the expression of PPARα and its target gene in AML-12 mouse hepatocytes was also examined. Key findings GD suppressed the elevated activities of serum transferases in GalN-induced liver injury in SD rats. The thiobarbituric acid reactive substance content in GalN-injured liver was a decreasing tendency by GD. GD suppressed the increased oxidized glutathione content, and increased the decreased protein, reduced glutathione contents, and catalase activity in GalN-injured liver. GD may improve the antioxidant defense system and protein synthesis in GalN-injured liver. GD suppressed the elevated expression of the genes related to the inflammation, and decreased the histopathological grade value of inflammatory cell infiltration in GalN-injured liver. GD increased the expression of PPARα protein in GalN-injured liver, and also increased the expression of PPARα and its target gene in AML-12 hepatocytes. The total and phosphorylated c-Met proteins in GalN-injured liver were the increasing tendencies by GD. Significance These findings indicate that GD has the hepatoprotective effect on GalN-induced liver injury in SD rats.

Significantly greater antioxidant anticancer activities of 2,3-dehydrosilybin than silybin

Silybin or silymarin extract has been used to treat liver diseases, and has now been entered into clinical trials for cancer treatment. Here, we compared antioxidant and anticancer activities between silybin and its oxidized form 2,3-dehydrosilybin (DHS). With IC 50 at three-fold lower concentrations than silybin, DHS inhibited reactive oxygen species generation in glucose–glucose oxidase system and HepG2 cells. Compared with silybin, DHS elicited greater protection against H 2O 2-induced HepG2 cell death and galactosamine-induced liver injury in vivo. It is known that oxidants induce releases of metalloproteinases (MMP)-2,-9 which are responsible for invasive and metastasis potentials of transformed cells. DHS at 10 μM markedly inhibited MMP-2,-9 releases as well as invasiveness, while silybin at 90 μM had marginal effects. DHS but not silybin at 30 μM induced apoptosis and loss of mitochondrial membrane potentials. LD 50 of DHS was five-fold lower than that of silybin. Our data suggest that DHS may be more useful therapeutically than silybin.

Galactosamine-Induced Acute Liver Injury in Rats Reduces Hepatic .ALPHA.-Tocopherol Transfer Protein Production

The liver plays the main role in the secretion of food-derived alpha-tocopherol into the circulation through the functioning of alpha-tocopherol transfer protein (alpha-TTP). However, the effect of liver disease on alpha-TTP level and alpha-tocopherol metabolism has not been clarified. We examined the amount of liver alpha-TTP and its effect on serum alpha-tocopherol concentration in liver injury. Male Wistar rats were injected intraperitoneally with D-galactosamine at 800 mg/kg body weight, and liver and serum lipid concentrations, alpha-tocopherol concentrations, and hepatic alpha-TTP mRNA and protein levels were measured at 24, 48, and 72 h after injection. On the basis of body weight changes and serum transaminase activities, the livers were found to be in an injured state 24 and 48 h after galactosamine injection but had recovered by 72 h. The hepatic alpha-TTP mRNA level was reduced throughout the experimental period, and at 48 h after injection the alpha-TTP protein level had begun to decrease. Lipid and alpha-tocopherol concentrations in the serum were decreased at 24 and 48 h after injection and increased at 72 h. Liver lipid concentrations were increased at 24 and 48 h after injection, but the liver alpha-tocopherol concentration was unchanged. These results show that galactosamine-induced liver injury decreases hepatic alpha-TTP synthesis in rats. Serum alpha-tocopherol concentration was not directly affected by the acute change in hepatic alpha-TTP level, suggesting that the chronic changes in alpha-TTP activity would be necessary to regulate serum alpha-tocopherol concentration.

Hepatoprotective Effects of Purple Potato Extract againstD-Galactosamine-Induced Liver Injury in Rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-alpha, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.

S-Adenosylmethionine but not glutathione protects against galactosamine-induced cytotoxicity in rat hepatocyte cultures

A gradual but extensive depletion of hepatic GSH has long been known to accompany development of galactosamine-induced hepatotoxicity in rats, and some protection from liver injury has been observed after administration of sulfhydryl-donating compounds. Although these observations support a key role for GSH in the underlying mechanism, the impact of GSH depletion and repletion on the hepatotoxic response to galactosamine is unclear. To investigate the role of GSH in galactosamine-induced liver injury, we examined the effect of modulating GSH content on galactosamine toxicity in rat primary hepatocyte cultures. Galactosamine (4 mM) cytotoxicity was assessed by release of lactate dehydrogenase into the culture medium, and hepatocellular GSH content was measured by HPLC with electrochemical detection. The data indicated that prior depletion of GSH with either diethyl maleate or buthionine sulfoximine significantly enhanced galactosamine toxicity; however, addition of GSH-ester or alternate sulfur nucleophiles at various times during the incubation did not abrogate toxicity. In contrast, co-addition of S-adenosylmethionine (SAMe) with galactosamine exerted a marked protective effect without significantly altering hepatocyte GSH content. These data suggest that GSH depletion is not directly involved in the sequelae for galactosamine-induced hepatotoxicity, and raise the possibility that SAMe may have hepatoprotective effects that are not dependent on its ability to enhance GSH synthesis.

Antioxidant activity of medicinal herb Rhodococcum vitis-idaea on galactosamine-induced liver injury in rats.

Aim of the study was to evaluate in vivo antioxidant action of medicinal herb Rhodococcum vitis-idaea (Rh.v) on galactosamine (GalN)-induced rat liver toxicity. The results showed that the hepatotoxicity and oxidative stress induced by GalN (700 mg/kg, s.c.) after 24 h evidenced by an increase in serum alanine aminotransferase and glutathione (GSH) S-transferase activities, and lipid peroxidation in liver homogenate were significantly inhibited, when 10 times diluted Rh.v. extract (5 ml/kg, i.p.) was given to rats 12 and 1 h before GalN treatment demonstrating that the extract of Rh.v is a potent antioxidant and protective against GalN-induced hepatotoxicity. The main antioxidant compound of the herb water extract used in the experiment was determined as arbutin, which possess 8% of dry weight of the herb. The electron spin resonance (ESR) spectrometer analysis revealed that the arbutin isolated from Rh.v exhibited strong superoxide and hydroxyl radical scavenging ability.

Oncotic necrosis and caspase-dependent apoptosis during galactosamine-induced liver injury in rats

The mode of cell death during galactosamine (Gal)-induced liver injury was originally thought to be oncotic necrosis but recently it was suggested to be apoptosis. Thus, the objective was to assess whether apoptosis and oncosis are sequential or independent events in the pathophysiology. In addition, the role of caspases in Gal-induced apoptotic signaling was investigated. A dose of 500 mg/kg Gal caused a time-dependent increase in plasma alanine transaminase (ALT) levels (24 h: 430 ± 122 U/L) in female Sprague–Dawley rats. This was accompanied by processing of procaspase-3 and significant increases in hepatic and plasma caspase-3 activities. Using morphology and TUNEL staining, apoptotic and oncotic cells were quantitated. The number of apoptotic hepatocytes increased from 0.14% in controls to 5.4 ± 1.0% 24 h after Gal treatment. In addition, the number of cells with oncotic morphology increased from 0 to 6.9% of total hepatocytes. Treatment with the pan-caspase inhibitor IDN-7314 (10 mg/kg) or pretreatment with uridine (1 g/kg), reduced all parameters of apoptosis to baseline. However, IDN-7314 administration did not affect plasma ALT activities and the number of oncotic cells at 6 h and only modestly reduced these parameters at 24 h. Uridine, on the other hand, prevented the increase of plasma ALT levels and reduced the number of apoptotic and oncotic cells by >80%. In conclusion, galactosamine-induced hepatocellular apoptosis in rats is caspase dependent. Although some of the apoptotic cells may undergo secondary necrosis, a significant number of hepatocytes die through oncotic necrosis as an independent mechanism of cell death.

Chronic alcohol exposure sensitizes mice to galactosamine-induced liver injury through enhanced keratinocyte chemoattractant and defective IL-10 production

Background/Aims: Alcohol sensitizes the liver to several injuries. The mechanisms leading to this sensitization are poorly defined. In the present study, we developed a mouse model of chronic exposure to alcohol vapours that sensitize mice to galactosamine (GAL) liver injury. Methods: C57BL/6 mice were exposed to ethanol vapours for 10 days. Liver injury was induced by intraperitoneal injection of GAL (1 g/kg) and mice were killed 24 h later. Results: GAL challenge after ethanol pre-treatment significantly raised serum alanine aminotransaminase (ALT) levels and enhanced liver inflammation when compared with the controls (GAL alone). Serum keratinocyte chemoattractant (KC) and monocyte chemoattractant protein-1 (MCP-1) levels were significantly increased in the GAL+ethanol group. On the contrary, serum interleukin 10 (IL-10) levels were lower than in controls. Anti-KC, anti-tumour necrosis factor α antibodies and intestinal decontamination significantly protected mice from liver injury. In GAL+ethanol-treated mice, IL-10 treatment reduced ALT release, KC and MCP-1 serum and hepatic mRNA levels, and improved liver inflammation. Conclusions: Enhancement of GAL-induced liver injury by ethanol is associated with an imbalance between proinflammatory cytokines and the anti-inflammatory cytokine IL-10 and depends on gut bacterial flora.

Preventive Effect of Dietary Nasunin on Galactosamine-Induced Liver Injury in Rats

The preventive effects of dietary nasunin on a liver injury induced by D-galactosamine (GalN) were investigated in rats. Increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities, which were induced by GalN, were suppressed by the feeding of nasunin before the intraperitoneal injection of GalN. Increases in liver oxidized-form glutathione (GSSG) concentration and the ratio of GSSG to reduced-form glutathione (GSH) by the injection of GalN were also suppressed by the dietary nasunin. A slight increase in the liver α-tocopherol concentration and an increase in the liver SOD activity due to the injection of GalN tended to return to the level of the control rat by the feeding of the nasunin. These results suggested that nasunin is effective to prevent liver injury and that it is also effective to prevent oxidative stress which may be induced by GalN-induced liver injury.

Kinetics of Expression of Connective Tissue Growth Factor Gene during Liver Regeneration after Partial Hepatectomy and [formula omitted]-Galactosamine-Induced Liver Injury in Rats

Connective tissue growth factor (CTGF) is up-regulated by TGF-β1 during wound healing. The present study examined the expression of CTGF during regeneration after 70% partial hepatectomy (PH) or d-galactosamine (GalN)-injured liver in rats. CTGF, TGF-β1, and type I collagen mRNAs were semiquantified by a ribonuclease protection assay. After PH, TGF-β1 and type I collagen were increased at 2–6 h and at 12–48 h. CTGF increased at 6 h and returned to the control level thereafter. The ribonuclease protection assay of cultured hepatic stellate cells (HSC) and in situ hybridization suggest that the cells express CTGF along sinusoid might be HSCs. After GalN administration, CTGF increased at 2–96 h with a shoulder peak at 6–12 h followed by a main peak at 24 h. TGF-β1 and type I collagen were up-regulated with kinetics similar to those of CTGF. The different kinetics between PH and GalN regenerations indicate that regulation of CTGF in the two processes is different. Higher TGF-β1 expression after inflammatory/necrotic process in the GalN regeneration may caused the prolonged CTGF expression.

Depletion of glutathione - a possible mechanism in galactosamine-induced liver injury

Depletion of glutathione - a possible mechanism in galactosamine-induced liver injury

Transforming growth factor-α expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming growth factor-α and hepatocyte growth factor

Transforming growth factor-α and hepatocyte growth factor are important stimulators of hepatocyte proliferation. In this series of experiments we sought to measure the expression of transforming growth factor-α mRNA by hepatocytes in response to toxic liver injury produced by carbon tetrachloride or galactosamine and to perform a more detailed analysis of transforming growth factor-α expression after partial hepatectomy. We also explored the interactions of transforming growth factor-α and hepatocyte growth factor in their effects on hepatocytes in vitro and tested the ability of these factors to stimulate endogenous transforming growth factor-α production by hepatocytes. In previous work we have used oligonucleotide probes to measure transforming growth factor-α mRNA expression after partial hepatectomy. In this study we used a rat transforming growth factor-α cDNA probe and found that the level of liver transforming growth factor-α mRNA increases 4 hr after partial hepatectomy, shows peak expression at 18 hr and returns to the normal level by 36 to 48 hr. Measurement of the corresponding peptide in the liver by means of radioimmunoassay shows that the level of transforming growth factor-α rises by 12 hr, peaks at 24 hr and remains significantly increased at 48 hr compared with the levels in sham-operated rats. Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively. After carbon tetrachloride administration the profiles of the transforming growth factor-α and hepatocyte growth factor mRNA expression are similar, each showing two peaks: the first at 12 hr and the second at 48 hr. In contrast, after galactosamineinduced liver injury the expression patterns of transforming growth factor-α and hepatocyte growth factor mRNAs differ: hepatocyte growth factor shows a major peak at 24 hr, with a smaller increase at 5 days, whereas transforming growth factor-α begins to increase after 2 days, with a single peak occurring at 5 days. In primary hepatocyte cultures, transforming growth factor-α and hepatocyte growth factor appear to have complementary effects. The maximal hepatocyte nuclear labeling index induced by hepatocyte growth factor was 42%; the addition of transforming growth factor-α increased this to 74%. Exogenous transforming growth factor-α, but not hepatocyte growth factor, stimulates the production of the transforming growth factor-α peptide by hepatocytes. However, when hepatocyte growth factor is added to cultures already containing transforming growth factor-α it further increases the amount of transforming growth factor-α-stimulated transforming growth factor-α synthesis by approximately 40%. These results strengthen the view that transforming growth factor-α is an important physiological stimulator of hepatocyte replication in liver growth induced by partial hepatectomy and toxic injury and that hepatocyte growth factor may modulate hepatocyte transforming growth factor-α secretion. (HEPATOLOGY 1993;18:1422–1431.)

Transforming growth factor-α expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming growth factor-α and hepatocyte growth factor

Transforming growth factor-alpha and hepatocyte growth factor are important stimulators of hepatocyte proliferation. In this series of experiments we sought to measure the expression of transforming growth factor-alpha mRNA by hepatocytes in response to toxic liver injury produced by carbon tetrachloride or galactosamine and to perform a more detailed analysis of transforming growth factor-alpha expression after partial hepatectomy. We also explored the interactions of transforming growth factor-alpha and hepatocyte growth factor in their effects on hepatocytes in vitro and tested the ability of these factors to stimulate endogenous transforming growth factor-alpha production by hepatocytes. In previous work we have used oligonucleotide probes to measure transforming growth factor-alpha mRNA expression after partial hepatectomy. In this study we used a rat transforming growth factor-alpha cDNA probe and found that the level of liver transforming growth factor-alpha mRNA increases 4 hr after partial hepatectomy, shows peak expression at 18 hr and returns to the normal level by 36 to 48 hr. Measurement of the corresponding peptide in the liver by means of radioimmunoassay shows that the level of transforming growth factor-alpha rises by 12 hr, peaks at 24 hr and remains significantly increased at 48 hr compared with the levels in sham-operated rats. Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively. After carbon tetrachloride administration the profiles of the transforming growth factor-alpha and hepatocyte growth factor mRNA expression are similar, each showing two peaks: the first at 12 hr and the second at 48 hr. In contrast, after galactosamine-induced liver injury the expression patterns of transforming growth factor-alpha and hepatocyte growth factor mRNAs differ: hepatocyte growth factor shows a major peak at 24 hr, with a smaller increase at 5 days, whereas transforming growth factor-alpha begins to increase after 2 days, with a single peak occurring at 5 days. In primary hepatocyte cultures, transforming growth factor-alpha and hepatocyte growth factor appear to have complementary effects. The maximal hepatocyte nuclear labeling index induced by hepatocyte growth factor was 42%; the addition of transforming growth factor-alpha increased this to 74%. Exogenous transforming growth factor-alpha, but not hepatocyte growth factor, stimulates the production of the transforming growth factor-alpha peptide by hepatocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Modification of Pathologic Changes in Toxicological Studies due to Endotoxin Derived from Intestinal Flora II. Effects on Galactosamine-induced Liver Injury with Lactulose, Cyclophosphamide, or Ricinoleic Acid in Rats

Modification of Pathologic Changes in Toxicological Studies due to Endotoxin Derived from Intestinal Flora II. Effects on Galactosamine-induced Liver Injury with Lactulose, Cyclophosphamide, or Ricinoleic Acid in Rats

Effect of galactosamine on hepatic carbohydrate metabolism: protective role of fructose 1,6-bisphosphate.

Intraperitoneal administration of galactosamine (400 mg/kg body wt) to rats results in reversible liver cell injury that is related to a dose-dependent depletion of uridine phosphates by formation of UDP-sugar derivatives. This damage was monitored through changes in serum enzymatic activities that increased after the first 6 hr of drug administration. Glycemia and serum albumin remained stable during liver injury, whereas cholesterol and triglycerides decreased. To maintain plasma glucose concentration, the hepatic carbohydrate metabolism was greatly altered. Glycogen dropped during the first hours, remaining low for up to 48 hr. Fructose 2,6-bisphosphate and ATP levels decreased even faster than glycogen, with lactate following a similar diminution and being restored in parallel with both metabolites. The reduction in fructose 2,6-bisphosphate can be explained by changes in the substrates or modulators of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase, because neither the cyclic AMP levels nor the activity ratio of the enzyme were modified. Simultaneous administration of galactosamine and fructose 1,6-bisphosphate (2 gm/kg) prevented liver cell death, as monitored by serum enzyme activities. Furthermore, the bisphosphorylated metabolite had protective effects on the changes in liver calcium content and ATP and fructose 2,6-bisphosphate concentrations. In contrast, fructose, fructose-1-phosphate and fructose-6-phosphate had no significant protection. Fructose 1,6-bisphosphate might decrease galactosamine toxicity by increasing fructose 2,6-bisphosphate and ATP levels, the changes in both metabolites probably being related. The significance of these findings with respect to the mechanism of galactosamine-induced liver injury is also discussed.

Mechanism of accumulation of macrophages in galactosamine-induced liver injury: effect of lipoxygenase inhibitors on chemotaxis of spleen cells.

In an attempt to clarify a mechanism of macrophage infiltration in galactosamine-induced hepatic injury, we investigated chemotactic factor(s) generated by murine hepatocytes exposed to galactosamine. Hepatocytes, isolated from murine liver by perfusion and digestion with collagenase, were incubated with galactosamine. Conditioned medium was collected 24 h later and chemotaxis of murine spleen cells was measured by stimulation of the conditioned medium using a modified Boyden chamber. Chemotactic activity was demonstrated in the conditioned medium of hepatocytes exposed to more than 3 mM galactosamine. Chemotactic activity of the conditioned medium was not reduced after freeze-thawing, and found to be dialyzable (molecular weight < 12,000). Trypsin (0.25%, 37 degrees C, 30 min) or heat (56 degrees C, 30 min) treatment reduced chemotactic activity of the conditioned medium. Furthermore, chemotaxis of spleen cells was decreased in the presence of lipoxygenase inhibitors (azelastine, ketotifen). These results suggest that accumulation of macrophages in the liver could be mediated by chemotactic factor produced by the galactosamine-treated hepatocytes, and that this mechanism may contribute to the pathogenesis of hepatic injury induced by galactosamine.

Experimental candidiasis associated with liver injury. Role of transferrin.

In an attempt to perform a further investigation on the proposal that an increasing susceptibility to Candida infection in liver injury may be related to unsaturated transferrin level (UIBC) and/or to a total amount of transferrin represented by TIBC, we conducted experimental candidiasis using mice with galactosamine-induced liver injury and investigated the effect of preadministration of transferrin prior to inoculation of Candida albicans. Final mortality was 10% in the mice without liver injury and without transferrin (Group 1) and ones with liver injury and with transferrin (Group 3). By contrast a 50% mortality was given in one only with liver injury (Group 2). The TIBCs in Groups 1 and 3 were significantly higher than that in Group 2. The UIBCs in Groups 2 and 3, although there was no significant difference between them, were significantly lower than that in Group 1. This study confirmed that transferrin (TIBC) may have a direct deterring effect on systemic Candida infection and the decreased TIBC in the liver injury enhances the growth of C. albicans.