Malondialdehyde In Liver Homogenates Research Articles

Influence of Derivatization Temperature and Butylated Hydroxytoluene on the Content of Malondialdehyde in Liver Homogenates

Influence of Derivatization Temperature and Butylated Hydroxytoluene on the Content of Malondialdehyde in Liver Homogenates

Biological Properties of Gynura procumbens Leaves Extract to MDA Levels and Antioxidant Activities in Liver of Mice

The objective of our research was to the evaluated biological activities of G. procumbens leaves methanol extract (GLME) for the hepatoprotective against cadmium (Cd) toxicity in mice. Research was performed using twenty five healthy male mice, which were grouped into five treatments: P1 (control), P2 (Cd-100mg/L), P3 (GLME-100mg/L+Cd-100mg/L), P4 (GLME-200mg/L+Cd-100mg/L), P5 (GLME-300mg/L+Cd-100mg/L). The results showed GLME contain phenolic and flavonoids compound by total phenolic content (TPC) and total flavonoid content (TFC) assay, they were strongly correlated with antioxidant activities. In this study, it was also known that Cd exposure increasing malondialdehyde (MDA) level and decreasing of superoxide dismutase (SOD) and catalase (CAT) activities in liver homogenates compared to control significantly. This is in line with a decreased in the number of normal cells and slightly an increased in damage cells in the histological hepatic cells. Administration of GLME can prevent liver cell damage due to Cd treatment by increasing the number of histological normal cells and the activities of SOD and CAT enzyme and reducing the level of MDA in liver homogenates. The best treatment of GLME was 100mg/L.

Effect of Chinese Herbal Monomer Hairy Calycosin on Nonalcoholic Fatty Liver Rats and its Mechanism

Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.

Effects of <i>Azadirachta indica</i> leaf aqeous extract on the antioxidant enzymes in paracetamol-induced hepatotoxicity in Wistar rats

Azadirachta indica, reported to be antioxidative, is hepatoprotective. This study evaluates the effect of A. indica leaf aqueous extract on antioxidant enzymes (glutathione peroxidase (GPx), superoxide dismutase (SOD) in paracetamol induced hepatotoxicity in Wister rats. Twenty four rats, in four groups, each containing six rats were used. Group A was given normal saline, group B paracetamol (800 mg/kg body weight) and groups C and D paracetamol and graded doses of the extract (400 mg and 800 mg/kg body weight respectively). The animals were weighed before and after experiment. Plasma liver enzymes (alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatases (ALP), plasma and liver homogenate malondialdehyde (MDA), GPx and SOD were estimated. Results showed significant weight increase (P<0.05) in A and D and weight loss in B. ALT, AST and ALP were significantly increased in B compared with A while C and D were decreased compared wth B. Plasma and homogenate MDA were increased while GPx and SOD were decreased in B compared wth A. Groups C and D MDA were decreased with increased GPx and SOD compared wth B. The extract could be a potent antidote to paracetamol induced hepatotoxicity as indicated by the increased GPx and SOD in C and D.Keywords: Azadirachta indica, hepatoxicity, paracetamol, malondialdehyde, antioxidant enzymes

Characterization and hepatoprotective activity of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar Eshu No. 8)

The hepatoprotective activity of anthocyanin-rich purple sweet potato extract (APSPE) was demonstrated. Sixty mice were randomly divided into six groups: control group [without carbon tetrachloride (CCl4) or APSPE]; model group (with CCl4 only); positive control group (50 mg/kg body weight silymarin); low-dose group (100 mg/kg body weight APSPE); medium-dose group (200 mg/kg body weight APSPE); and high-dose group (400 mg/kg body weight APSPE). After 10 days intragastric administration of the respective supplements, the mice in all groups except control were injected intraperitoneally with CCl4 (0.15% in arachis oil, 10 mL/kg body weight, intravenous). Twelve hours after CCl4 injection, the mice were measured in terms of liver index, levels of aspartate aminotransferase and alanine aminotransferase in serum, as well as glutathione, superoxide dismutase, and malondialdehyde in liver homogenate. Additionally, the livers of mice were stained with hematoxylin and eosin and sectioned for observation. Nineteen purple sweet potato anthocyanins were identified from the purple sweet potato cultivar Eshu No. 8 and analyzed by liquid chromatography– electrospray ionization–tandem mass spectrometry. Peonidin 3-coumaryl-p-hydroxybenzoyl sophoroside-5-glucoside was first identified in purple sweet potato. The results showed that anthocyanins in Eshu No. 8 had good hepatoprotective activity.

Protective effect of astragaloside IV against acute liver failure in experimental mice

Objective: To investigate the clinical effect of astragaloside IV in the early treatment of mice with acute liver failure and possible mechanisms. Methods: A mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS) was established, and the mice were given astragaloside IV at different doses. The survival rate of mice, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histopathological changes, apoptosis of hepatocytes, and the expression of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in each group. The least significant difference test was used for data with homogeneity of variances, the Dunnett's T3 test was used for data with heterogeneity of variance, and the Kaplan-Meier method was used for survival analysis. Results: Compared with the model group, the high-dose astragaloside IV group had a significant increase in the 48-hour survival rate [60% (9/15) vs 13.3% (2/15), P < 0.05], significant reductions in the serum ALT and AST levels (P < 0.01), and significant reductions in liver histopathological indices and the degree of apoptosis of hepatocytes (P < 0.01), as well as a significant reduction in the content of MDA in liver homogenate (P < 0.01) and a significant increase in the activity of SOD (P < 0.05). Conclusion: High-dose astragaloside IV has a significant protective effect against D-GalN/LPS-induced acute liver injury in mice, and its mechanisms may be associated with its effects against cell apoptosis and oxidative damage.

Species differences in methotrexate-induced hepatotoxicity and nephrotoxicity: Rabbits resist methotrexate nephrotoxicity

Background: Animal models are important tools for studying drug-induced toxicity. Species differences in drug-induced nephrotoxicity or hepatotoxicity was frequently reported, however, clear evidence of species differences in nephrotoxicity or hepatotoxicity induced by methotrexate (MTX) is not available. Aim: The present study was designed to investigate nephrotoxicity or hepatotoxicity of MTX in mice and rabbits. Methodology: twelve rabbits and 16 mice were used for the study. Each species of animals was divided into 2 groups; control and MTX treatedgroups. The control groups were treated with normal saline intra-peritoneum (IP), MTX was given IP in a dose of 20 mg/kg/weekly for 38 days for the rabbits and at a dose of 10mg/kg/ weekly for 23 days for mice. Serum levels of liver enzymes, urea, creatinine, Malondialdehyde (MDA) and MDA in liver homogenate were estimated for the rabbits. In mice, glutathione (GSH) and MDA were estimated in liver and kidney homogenates. Histopathological examination of the kidney and liver was done for the 2 species. Results: In the rabbits, MTX resulted in a significant increase in liver enzymes, and in MDA levels of serum, liver and kidney homogenates, while the levels of urea and creatinine were not affected. Histopathological changes suggestive of liver damage were seen, while the kidneys appeared normal on histopathological examination. In the mice, MTX resulted in a significant increase in MDA in the liver homogenates with a small and insignificant reduction in GSH. In mice kidney homogenates, MTX had not affected MDA, while GSH was significantly reduced. Histopathological examination in mice showed significant damage in both liver and kidney. Conclusion: MTX produced hepatotoxicity in rabbits and mice but nephrotoxicity occurred in mice only. This suggests that rabbits might be resistant to MTX induced nephrotoxicity

Protective effects of C-phycocyanin on alcohol-induced subacute liver injury in mice

Excessive and long-term alcohol consumption leads to liver disease and low immunity. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Arthrospira (Spirulina) platensis, exerts protective effects against chemical-induced organ damage and improves immunity. In this study, we investigated whether C-PC could protect against ethanol-induced subacute liver injury and improve immunity. KM mice with ethanol-induced liver injury were established, and animals were divided into three groups that were treated with high, medium, and low doses of C-PC. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), total bilirubin (TBIL), liver homogenate malondialdehyde (MDA), and superoxide dismutase (SOD) levels were measured. In addition, the number of thymus T cell subsets was assessed, and liver sections were examined pathologically. C-PC exhibited obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL, and MDA levels and increased SOD content significantly in the liver. C-PC also increased serum CD3+ and CD4+ cell activation and T cell proliferation significantly compared with the model group. The structure of the hepatic lobules was clear, the liver sinus returned to normal, and the liver cell cords were arranged in neat rows. Therefore, C-PC could protect against ethanol-induced subacute liver injury significantly.

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 effects 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 effects 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.

Hepatoprotective effect of juglone on dimethylnitrosamine-induced liver fibrosis and its effect on hepatic antioxidant defence and the expression levels of α-SMA and collagen III.

The present study aimed to investigate the antifibrotic effects of juglone on dimethylnitrosamine (DMN)-induced fibrosis in rats. Juglone, which is a quinone, significantly decreased DMN-induced rat hepatic fibrosis, which was associated with increased superoxide dismutase (SOD) activity, decreased oxidative stress and reduced levels of α-smooth muscle actin (α-SMA) and collagen (Col) III in the liver. Serum levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type III precollagen and type IV collagen were significantly reduced by treatment with juglone. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injections of DMN solution and hepatic fibrosis was assessed using Massonstrichome staining. The expression levels of α-SMA and Col III were determined using immunohistochemical techniques. The activities of SOD and malondialdehyde in liver homogenates were also determined. The results suggested that juglone augmented the antioxidative capability of the liver, possibly by stimulating the activity of SOD, which promoted the inactivation of hepatic stellate cells (HSCs) and decreased the accumulation of extracellular matrix collagen in the liver, thereby alleviating hepatic fibrosis. Silymarin was used as a positive control for liver fibrosis protection. It was hypothesized that juglone alleviates or mitigatesoxidative stress-mediated hepatic fibrosis by upregulating the expression of peroxisome proliferator-activated receptor γ and inhibiting the activation of HSC.

Protective effects of capillary artemisia polysaccharide on oxidative injury to the liver in rats with obstructive jaundice

Obstructive jaundice is a condition caused by blockage of the flow of bile out of the liver. This results in an overflow of bile and its by-products into the blood, and bile excretion from the body is incomplete. Untreated, obstructive jaundice can lead to serious infection that spreads to other parts of the body. We examined the protective effect of capillary artemisia polysaccharide on oxidative damage to the liver in growing rats with obstructive jaundice (OJ). Growing male Wistar rats (n=40, age 3–4 weeks) were randomly divided into four groups (n=10 in each group): normal control group, sham group, OJ group and OJ with capillary artimesia polysaccha-ride treatment group (study group). The rats of the OJ group and the study group were subjected to common bile dust ligation, while the sham group had the bile duct mobilized but not ligated. The rats of the study group recieved 5 ml/kg capillary artimesia polysaccharide (0.5 g/ml) by intraperitoneal (i.p.) injection once daily while the other groups were administered 5 ml/kg saline by i.p. injection. After 4 weeks, the rats were sacrificed to obtain liver weight and to compute the liver coefficient. Additional measures included liver homogenate malondialdehyde (MDA) and the activity levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The liver weight and liver coefficient of rats in the study group were lower than those in the OJ group and higher than those in the control and sham groups (P<0.05). Liver homogenate MDA content in the study group rats was lower than that in the OJ group and higher than that in the control and sham group (P<0.05). SOD, GSH-Px and CAT activities were higher in the study group rats than those in the OJ group and lower than those in other groups (P<0.05). Capillary artimesia capillary artemisia polysaccharide protects the liver from oxidative damage and improves antioxidant defense in growing rats with obstructive jaundice.

Study of potential protective effects of blueberry on hepatic cytochrome P450 2E1 expression in rats with immune hepatic fibrosis

To study the protective effects of blueberry against rat immune hepatic fibrosis, specifically through the expression of hepatic cytochrome P450 2E1. Fifty Wistar rats were randomly divided into five study groups (n = 10 each): Group A: normal control group, Group B: hepatic fibrosis model group, Group C: preventive group administered blueberry juice, Group D: preventive group administered Fu-Fang-Bie-Jia-Ruan-Gan tablet, and Group E: preventive group administered a combination of blueberry juice and Fu-Fang-Bie-Jia-Ruan-Gan tablet. The hepatic fibrosis model was established by intraperitoneal injection of porcine serum once daily for 12 weeks. Simultaneously, rats in preventive groups (Groups C-E) were perfused with blueberry juice or Fu-Fang-Bie-Jia-Ruan-Gan tablet or combinations of blueberry juice and Fu-Fang-Bie-Jia-Ruan-Gan tablet, respectively, for 12 weeks. The normal control group was perfused with saline for 12 weeks. All animals were sacrificed at the end of the 12 weeks, and serum levels of alanine aminotransferase (ALT) were measured and activities of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (Hyp) in liver homogenates were determined. Pathology of hepatic fibrosis was evaluated by hematoxylin-eosin (HE) and Masson staining. Expression of CYP2E1 was detected by real-time RT-PCR, immunohistochemical techniques, and Western blotting. Serum ALT levels were not significantly different in the control and treatment groups (F=4.056, P more than 0.05): A: 37.87+/-4.53 U/L, B: 49.23+/-9.81 U/L, C: 39.94+/-6.32 U/L, D: 40.50+/-5.70 U/L, and E: 38.24+/-8.43 U/L. Compared with Group B, the pathological stages of hepatic fibrosis were significantly reduced in the prevention groups (C-E) (F=95.097, P less than 0.05). Hyp and MDA in liver homogenates of groups C-E were significantly lower than those of Group B (Hyp: C: 472.68+/-44.14 mug/g, D: 416.12+/-39.38 mug/g, E: 429.51+/-55.14 mug/g vs. B: 603.16+/-68.92 mug/g, F=39.315, P less than 0.05; MDA: C: 0.83+/-0.06 nmol/mg, D: 0.96+/-0.08 nmol/mg, E: 0.85+/-0.06 nmol/mg vs. B: 1.24+/-0.15 nmol/mg, F=46.376, P less than 0.05). In contrast, SOD activities in Group C-E were significantly higher than those in Group B (C: 2.47+/-0.38 U/mg, D: 1.95+/-0.45 U/mg, E: 2.16+/-0.23 U/mg vs. B: 1.56+/-0.41 U/mg, F=25.557, P less than 0.05). Compared with Group A, the mRNA and protein expressions of CYP2E1 were increased in groups B-E, however the differences did not reach statistical significance (mRNA: F=0.897, protein: F=0.492, both P more than 0.05). The mRNA and protein expressions of CYP2E1 in groups C-E were lower than those of Group B, however the differences did not reach statistical significance (mRNA: F=0.897, protein: F=0.492, P more than 0.05). Blueberry exhibits certain protective effects against porcine serum-induced hepatic fibrosis in rats. The expression of hepatic cytochrome P450 2E1 in rats with immune hepatic fibrosis is not significantly different from the normal rats. Blueberry has no effect on the expression of hepatic cytochrome P4502E1.

Effect of magnesium isoglycyrrhizinate on PLA2 during liver tissue injury following limb ischemia/reperfusion in rats

To investigate the effects of magnesium isoglycyrrhizinate (MI) on the changes of phospholipase A2 (PLA2) induced during liver tissue injury following limb ischemia/reperfusion (I/R) in rats. Twenty-four healthy male Sprague-Dawley rats weighing (230+/-30) g were randomly divided into three groups (n = 8 each) as follows: control (Group C: anesthetization without any ischemia); I/R injury (Group I/R: 4 h ischemia induced by rubber band ligation of the left hind limb around the roots of the hind limb, followed by 6 h of reperfusion, with 1 mL normal saline given via tail vein prior to reperfusion); MI-treated group (Group MI: underwent ischemia and reperfusion, with 1 mL MI (30 mg/kg) infused prior to reperfusion). Levels of TNFa and PLA2 in plasma and liver tissue were measured by enzyme-linked immunosorbent assay (ELISA). Levels of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), myeloperoxidase (MPO), and malondialdehyde (MDA), and activities of MPO and MDA in liver tissue were measured by colorimetry. Ultrastructural changes of liver tissue were observed by electron microscopy. The MI group had significantly lower PLA2 and TNFa in liver homogenates and serum than the I/R group (both P less than 0.05). Serum ALT, AST, LDH, and CK were significantly lower in the MI group than in the I/R group (all P less than 0.05), as were the levels of MPO and MDA in liver homogenates and serum (all P less than 0.05). The I/R group showed significantly more liver tissue damage, which appeared to be attenuated in the MI group. MI treatment can inhibit the I/R-induced TNFa, PLA2, and MDA in plasma and liver tissue, as well as decrease the I/R-induced MPO activity in rats. Thus, MI may have protective effects against liver tissue injury following limb ischemia/reperfusion.

Effects of blueberry on hepatic fibrosis and ultrastructural of hepatocytes in rats

To observe the effects of blueberry on rat with hepatic fibrosis and ultrastructural. of hepatocytes. Sixty (60) healthy Wistar rats were randomly divided into six groups: normal control group (group A), hepatic fibrosis model group (group B), blueberry at low, middle and high concentration groups (group C, D, E), Fu-Fang-Bie-Jia-Ruan-Gan tablet group (group F). The hepatic fibrosis model of rat was established by intraperitoneal injection of porcine serum once daily for 12 weeks. Simultaneously, rats in groups C-F were respectively perfused with blueberry juice or Fu-Fang-Bie-Jia-Ruan-Gan tablet for 12 weeks except for the normal control group which accepted saline alone. Upon terminal sacrifices of all rats at the end of the twelve weeks. Pathology of hepatic tissue was evaluated by hematoxylin-eosin (HE), Masson staining and transmission electron microscope. Liver index were measured. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were examined. Activities of superoxide dismutase (SOD), the contents of malondialdehyde (MDA), hydroxyproline (Hyp) and reduced glutathione (GSH) in liver homogenates were determined. Refer to the serum levels of ALT and AST, there is no significant difference existed in all groups (P > 0.05). Activities of SOD, the contents of GSH in liver homogenates of group D and E were significantly higher than those of group B(P < 0.05), while liver index, the contents of Hyp, MDA in liver homogenates were significantly lower than those of group B (P < 0.05). Compared with the group B, the pathological stages of hepatic fibrosis in group D and E were significantly reduced (P < 0.05), the expression of collagen were decreased, ultrastructural alterations were markedly improved. Blueberry may have certain preventional protective effects on porcine serum induced rat hepatic fibrosis and exhibit certain protective effects on organelles of hepatocytes (such as mitochondria), especially in middle and high does of blueberry. Its mechanism is probably related to increase the ability of antioxidant stress by increasing SOD activity and GSH content and reducing MDA content.

Role of JNK signal transduction pathway in nonalcoholic fatty liver disease

To investigate the role of c-Jun N-terminal kinase (JNK) signal transduction pathway in the rats of nonalcoholic fatty liver disease (NAFLD). Sixty four Sprague-Dawley rats were randomly divided into four groups: 8-week control group (NG8w), 12-week control group (NG12 w), 8-week high-fat diet (HG8w), and 12-week high-fat diet group (HG12w), with 16 rats in each group. Glucose infusion rate (GIR) was tested by euglycemic hyperinsulinemic clamp; aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), free fatty acid (FFAs), fast insulin (FIns), tumor necrosis factor alpha (TNF alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were tested by biochemistry automatic analyzer or RIA; The expression of JNK1, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 Ser307 (p-IRS-1 Ser307), Protein kinase B (PKB) and phospho-PKB Ser473 (p- PKB Ser473) were detected by Western blot. Compared to control group, body weight, liver index, serum levels of ALT, AST, TG, TC, FIns, FFAs, TNF alpha, and TC, TG FFAs, MDA in liver homogenates were increased, while the level of SOD, and GIR were decreased. The expression of JNK1 protein and p-IRS-1 Ser307 in liver tissue was up-regulated, while expression of p-PKB Ser473 was decreased (P < 0.05). A positive correlation was found between the expression intensity of JNK1 and IR (Pearson correlation: 0.718, P < 0.01). The high-fat could induce the expression of JNK1, which in turn modulates the phosphorylation of proteins in the insulin signaling pathway, and induces insulin resistant.

Peroxisome proliferator activated receptor-gamma in pathogenesis of experimental fatty liver disease.

To study the expression of peroxisome proliferator activated receptor-gamma (PPARgamma) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARgamma in the pathogenesis of FLD to provide the basis for using PPARgamma ligand to treat patients with FLD. Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFalpha) in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan IV, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope. The expression of PPARgamma in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARgamma and biochemical indexes, and liver histology were analyzed. The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups, especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARgamma was decreased remarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43+/-1.48) was significantly lower than that in normal group (18.34+/-3.73), alcohol group (8.82+/-2.52) and fat-rich diet group (11.73+/-2.51) (all P<0.01). The level of PPARgamma mRNA was also lower in the livers of model rats (group B-D) than in livers of controls. The expression of PPARgamma in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFalpha and the content of MDA in liver homogenates, but not with steatosis or serum ALT. Decreased expression of PPARgamma may play an important role in the development of hepatocellular inflammation, necrosis and fibrosis of rats with FLD. Thus, activating PPARgamma by its ligand can be anticipated to provide a therapy target for FLD.

Hepatocellular oxidative stress and initial graft injury in human liver transplantation

Background/Aims: The mechanisms underlying the initial graft dysfunction in liver transplantation are not completely understood, although much of the liver graft injury derives from the ischemia/reperfusion-induced oxidative stress. Thus, the purpose of our study was to determine the involvement of oxidative stress in the initial graft dysfunction in human liver transplantation. Methods: Liver biopsies were taken at different times of the transplantation procedure, at the organ donor laparatomy (T1), before graft reperfusion (T2), and 5–60 min after graft reperfusion (T3), determining the levels of GSH, GSSG, as well as peroxides and malondialdehyde in liver homogenates. Results: Patients were graded into two groups depending on whether the peak serum alanine aminotransferases within the first 3 postoperative days were lower (group A, mild to moderate injury: 32 patients) or higher (group B, severe injury: 5 patients) than 2500 U/l. The levels of GSH at time intervals T1-T3 were similar for groups A and B, with a trend to lower GSSG levels in group B at T2 and T3 samples. This outcome was accompanied by unchanged levels of malondialdehyde and hydrogen peroxide in the same samples in both groups of patients. No patient developed primary graft nonfunction. One-year cumulative survival was 81% and 60% in groups A and B, respectively ( p>0.05). Conclusions: These findings indicate a lack of significant generation of reactive oxygen species and consequent oxidative stress as a major factor involved in the pathogenesis of the initial graft dysfunction in human liver transplantation.