Effect of Vitamin E on Serum Aminotransferase and Thioredoxin Levels in Patients with Viral Hepatitis C

Objectives: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. Methods: Seventeen HCV patients (male=3; female=14) of age 62±7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-α´-tocopherol 500?mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients “T”, low ALT group “L” (ALT<70?IU/l) and high ALT group “H”(ALT>70?IU/l), respectively.Results: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p<0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p<0.0001) from the 1st to 3rd month in all three T, H and L groups. Conclusion: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels >70?IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.     

Vitamin E Improves the Aminotransferase Status of Patients Suffering from Viral Hepatitis C: A Randomized,Double-Blind,Placebo-Controlled Study

Vitamin E has been shown to protect against liver damage induced by oxidative stress in animal experiments. Based on our previous findings of diminished vitamin E levels in patients suffering from viral hepatitis, we treated 23 hepatitis C patients refractory to a-interferon therapy with high doses of vitamin E (2 × 400 IU RRR-α-tocopherol/day) for 12 weeks. Study design: pro-spective randomized double-blind crossover design. Clinical parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined for monitoring the disease state, in parallel vitamin E plasma levels and plasma lipids were determined. The plasma levels of the a-tocopherol were increased about 2-fold in all 23 patients. In 11 of 23 patients the clinical parameters indicative of liver damage were improved during the phase of vitamin E treatment (48% responders). ALT levels in responders were lowered by 46% and AST levels were lowered by 35% after 12 weeks of vitamin E treatment. Cessation of vitamin E treatment was followed by a rapid relapse of ALT and AST elevation, whereas retreatment led to a reproducible ALT decrease by 45% and AST decrease of 37% after a 6 months followup. Since vitamin E is non-toxic even at elevated doses ingested over extended periods, we suggest the treatment of patients refractory to α-interferon therapy suffering from hepatitis C with vitamin E as a supportive therapy.     

Protection against CCl4-induced injury in liver by adenovirally introduced thioredoxin gene

Antioxidation therapy is a promising strategy for treating or preventing oxidative stress-related liver diseases. The human thioredoxin (TRX) gene was inserted into an adenovirus vector (Adv-TRX), which was administered to mice. The mice were treated with 1 ml/kg CCl4 48 h after the infection. Blood samples were taken and the liver was excised 24 h after the CCl4 treatment. Serum ammonia, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined, and liver sections were stained with hematoxylin and eosin. RT-PCR analysis showed that the introduced TRX gene was expressed only in the liver. Adv-TRX decreased the serum ammonia, AST, and ALT levels. Hematoxylin-eosin staining indicated that the CCl4-induced injury was significantly prevented by the Adv-TRX infection. The gene delivery of TRX, which plays a central role in intracellular redox control, was shown to be effective in protecting the liver against oxidative stress-induced injury.     

Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

Aims

Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.

Methods

Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.

Results

The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p<0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1β (p<0.05), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-2′-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration.

Conclusions

The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.     

A combination of ascorbic acid and α-tocopherol or a combination of Mg and Zn are both able to reduce the adverse effects of lindane-poisoning on rat brain and liver

The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of supplementation with ascorbic acid (Vit C) and α-tocopherol (Vit E) or with Mg and Zn upon lindane-induced damages in liver and brain. Under our experimental conditions, lindane poisoning (5 mg/kg body weight per day for 3 days) resulted in (1) an increased level of plasma glucose, cholesterol and triglycerides, (2) an increased activity of LDH, ALP, AST, ALT, (3) an oxidative stress in liver and brain as revealed by an increased level of lipids peroxidation (TBARS) and a decrease of glutathione-peroxidase, superoxide dismutase and catalase activities in liver and brain. In conclusion, both Vit C + E or Mg + Zn treatments display beneficial effects upon oxidative stress induced by lindane treatment in liver and brain.     

Limited Utility of Plasma M30 in Discriminating Non-Alcoholic Steatohepatitis from Steatosis – A Comparison with Routine Biochemical Markers

Introduction

The utility of Cytokeratin-18 fragment, namely CK18Asp396 (M30), for the diagnosis of non-alcoholic steatohepatitis (NASH) is currently uncertain. We aimed to provide further data in this area among multi-ethnic Asian subjects with NAFLD.

Materials and Methods

The accuracy of M30 for detecting NASH was compared with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (GGT) levels in consecutive adult subjects with biopsy-proven non-alcoholic fatty liver disease (NAFLD).

Results

Data for 93 NAFLD subjects (mean age 51.0±11.1 years old and 51.6% males) and 20 healthy controls (mean age 50.2±16.4 years old and 33.3% males) were analyzed. There were 39 NASH subjects (41.9%) and 54 non-NASH subjects (58.1%) among the NAFLD subjects. Plasma M30 (349 U/L vs. 162 U/L), and serum ALT (70 IU/L vs. 26 IU/L), AST (41 IU/L vs. 20 IU/L) and GGT (75 IU/L vs. 33 IU/L) were significantly higher in NAFLD subjects than in healthy controls. Serum ALT (86 IU/L vs. 61 IU/L), AST (58 IU/L vs. 34 IU/L) and GGT (97 IU/L vs. 56 IU/L) were significantly higher in NASH subjects compared to non-NASH subjects, but no significant difference was observed with plasma M30 (435 U/L vs. 331 U/L). The accuracy of plasma M30, and serum ALT, AST and GGT was good for predicting NAFLD (AUROC 0.91, 0.95, 0.87 and 0.85, respectively) but less so for NASH (AUROC 0.59, 0.64, 0.75 and 0.68, respectively). Serum ALT and AST, but not plasma M30 showed a significant trend with increasing grades of ballooning and lobular inflammation.

Conclusion

The utility of M30 in the detection of NASH in clinical practice appears limited, in comparison to routine biochemical markers.     

Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

BACKGROUND: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats

Vitamin D, most commonly associated with the growth and remodeling of bone, has been shown to ameliorate ischemia/reperfusion injury (IRI) in some tissues, yet its underlying mechanism remains elusive. This study was designed to examine the protective effect of vitamin D, if any, against hepatic IRI in rats and the underlying mechanism involved. Adult female Wistar rats were randomly divided into control, sham-operated (sham), ischemia/reperfusion (I/R), and ischemic-reperfused vitamin D-treated (vit D) groups. Rats in the I/R and vit D groups were subjected to partial (70 %) hepatic ischemia for 45 min, followed by 1 h of reperfusion. Vitamin D was given to rats orally in a dose of 500 IU/kg daily for 2 weeks before being subjected to I/R. Markers of liver damage, oxidative stress, inflammation and apoptosis were evaluated. Hepatic morphology was also examined. Vit D-treated rats had significantly lower serum levels of alanine aminotransferase, aspartate aminotransferase, and γ glutamyl transferase compared to rats in the I/R group. Also, vit D-treated rats showed a significant decrease in malondialdehyde, interleukin-1 beta, interleukin-6, tumor necrosis factor-α, nuclear factor κB, B cell leukemia/lymphoma 2-associated X protein, cytochrome c, and caspase-3 levels, with higher levels of glutathione peroxidase and B cell lymphoma 2 protein levels in liver tissues compared to I/R rats. Histological examination showed less damaged liver tissues with amelioration of apoptotic signs in the vit D group compared to the I/R group. In conclusion, vitamin D supplementation ameliorates hepatic IRI mostly by alleviating the inflammatory-apoptotic response mediated by the oxidative reperfusion injury insult.     

Blood antioxidant status and urinary levels of catecholamine metabolites in beta-thalassemia.

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.     

Effect of Caffeine-Containing Beverage Consumption on Serum Alanine Aminotransferase Levels in Patients with Chronic Hepatitis C Virus Infection: A Hospital-Based Cohort Study

Introduction

To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months.

Materials and Methods

From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients’ medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L).

Results

Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction.

Conclusion

Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels.     

Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence

Background & Aims

There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding.

Methods

A total of 975 school children (aged 7–18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls.

Results

In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor.

Conclusions

In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.     

Cellular functions and transcriptional regulation of a third thioredoxin from Schizosaccharomyces pombe

The structural gene encoding a third thioredoxin (Trx) homologue, TRX3, of the fission yeast Schizosaccharomyces pombe was characterized and its regulation was studied. The determined DNA sequence encoded a putative 290 amino acid sequence of Trx with a molecular mass of 31,889 Da. The TRX3 mRNA level was increased in S. pombe cells harboring plasmid pTRX3, suggesting that the cloned TRX3 gene was functional. Yeast cultures harbouring plasmid pTRX3 exhibited shorter generation times and higher survival on solid minimal media plates incorporating mercury chloride (0.01 mmol/L) or hydrogen peroxide (1 mmol/L) compared with control cultures. Yeast cells containing extra copies of TRX3, but not TRX1 and TRX2, gave rise to lower reactive oxygen species levels than control cells. Oxidative stress owing to hydrogen peroxide and menadione enhanced the synthesis of beta-galactosidase from the TRX3-lacZ fusion gene in Pap1-positive cells but not in Pap1-negative cells. The TRX3 mRNA level was increased by oxidative stress only in Pap1-positive cells. Basal expression of the TRX3 gene also depended on Pap1. We concluded that S. pombe TRX3 is linked with yeast growth and oxidative stress response, with its expression being regulated by oxidative stress in a Pap1-dependent manner.     

Preventive effect of omega-3 fatty acids in a rat model of stress-induced liver injury

Omega-3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega-3 fatty acids related to acute cold-restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega-3 group, each rat was pretreated with omega-3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega-3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase-3. Results showed that pretreatment of stressed rats with omega-3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF-α. Also, they improved liver damage and suppressed hepatic caspase-3 expression. In conclusion, pretreatment of stressed rats with omega-3 fatty acids has ameliorated stress-induced liver damage due to their antioxidant, anti-inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.     

Protective effects of ascorbic acid on hepatotoxicity and oxidative stress caused by carbon tetrachloride in the liver of Wistar rats

This study was planned to investigate the protective effect of l (+)‐ascorbic acid (Vit C) on CCl₄‐induced hepatotoxicity and oxidative stress in the liver of Wistar rats (Rattus Norvegicus, strain Wistar). Twenty‐four adult male Wistar rats were fed with standard rat chow diet for 10 days and randomly were divided into four groups of six each as follows: (1) control, (2) CCl₄, (3) “CCl₄ + Vit C”, (4) Vit C groups. CCl₄ was applied to rats belonging to CCl₄ and “CCl₄ + Vit C” groups subcutaneously at 1 mg kg^?1 dose CCl₄ for 3 days. Vit C applied to “CCl₄ + Vit C” and “Vit C” group rats intraperitoneally at 300 mg kg^?1 dose for 3 days. All rats were sacrificed and livers were quickly removed on the fourth day of the experiment. MDA, total glutathione (T.GSH) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐PX) activities were measured in the liver of all groups of rats and also serum alanine amino transferase (ALT) and aspartate amino transferase (AST) activities were detected to determine liver functions in all groups of rats. Histopathological changes were evaluated by light and transmission electron microscopes. In “CCl₄ + Vit C” group, MDA level was significantly decreased (p < 0.05) and SOD, CAT, GSH‐PX activities were significantly increased (p < 0.005, 0.01, 0.05) respectively, T.GSH level was significantly increased (p < 0.005) and serum ALT and AST activities were significantly decreased (p < 0.01, 0.05), respectively, when compared with CCl₄ group. These results show that Vit C has a highly protective effect on hepatotoxicity and oxidative stress caused by CCl₄. Copyright © 2009 John Wiley & Sons, Ltd.     

High Hepatitis B Surface Antigen Levels Predict Insignificant Fibrosis in Hepatitis B e Antigen Positive Chronic Hepatitis B

Introduction

There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB).

Methods

Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation.

Results

140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology.

Conclusion

Among HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.     

Caspase-12抑制剂对百草枯中毒大鼠肝损伤的保护作用

目的:观察caspase-12抑制剂Z-ATAD-FMK对百草枯染毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡的影响,以及通过血清SOD和MDA的检测,探讨其对百草枯中毒大鼠肝脏保护作用和对机体氧化应激反应的作用。方法:50只健康Wistar大鼠随机分三组:A组为正常对照组;B组为模型组(PQ染毒);C组抑制剂组(PQ/Z-ATAD-FMK),于3d、7d处死B组和C组各10只大鼠。取血检测ALT、TBIL、SOD和MDA;HE染色观察肝组织病理学变化;免疫组化法检测caspase-12蛋白;二苯胺法检测细胞凋亡率。SPSS18.0统计分析。结果:Z-ATAD-FMK抑制剂组ALT、TBIL、MDA值低于模型组(P0.05),SOD高于模型组(P0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P0.05);HE染色显示凋亡和坏死程度也较模型组轻。结论:Caspase-12抑制剂Z-ATAD-FMK能减少百草枯中毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对肝脏具有保护作用,同时可以抑制百草枯中毒大鼠的氧化应激反应。     

Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver

Nitrosamine compounds are known hepatic carcinogens. In the metabolism of nitrosamines, such as N-nitrosodiethylamine (NDEA), there is evidence of the formation of reactive oxygen species (ROS) resulting in oxidative stress, which may be one of the factors in the etiology of cancer. The formation of ROS may alter the antioxidant system, while the presence of Vitamin E may counteract NDEA induced oxidative stress. This study was planned to determine whether pre-treatment with Vitamin E (40 mg/kg body weight, i.p., twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress in liver caused by the carcinogen. A single necrogenic dose of NDEA (200mg/kg body weight) was administered i.p. to the male albino rats with or without Vitamin E pre-treatment and the animals were sacrificed on Days 7, 14 or 21 after the administration of NDEA. The result showed enhanced levels of hepatic lipid peroxidation (LPO) and conjugated dienes of NDEA treated rats as the indices of oxidative stress, however, Vitamin E pre-treated rats administered NDEA showed decreased LPO and conjugated dienes (Day 21). Superoxide dismutase (SOD) activity in liver was not altered significantly in NDEA treated rats with or without Vitamin E pre-treatment. Catalase (CAT) activity was inhibited with NDEA treatment, however, Vitamin E pre-treatment showed recovery in hepatic CAT activity (Days 14 and 21). Total and Se-glutathione peroxidase (GSH-Px) activities and glutathione-S-transferase (GST) activity in liver increased in NDEA treated rats irrespective of Vitamin E pre-treatment. Glutathione reductase (GSH-R) activity as well as total glutathione (GSH) content in liver decreased in NDEA treated animals, both of which were recovered in Vitamin E pre-treated rats administered NDEA. Activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were increased significantly following NDEA treatment to rats with or without Vitamin E pre-treatment. The activities of AST and ALT enzymes were significantly reduced on Days 14 and 21 and ALP activity was reduced on Day 21 in NDEA+Vitamin E treated animals when compared to NDEA treated alone. LDH enzyme activity was normalized on Day 14 in Vitamin E pre-treated animals administered NDEA. However, the AST, ALT and ALP enzyme activities remained high in all treatment groups as compared to control group. Normal control and Vitamin E treated alone rats revealed normal histology of liver. On the other hand, NDEA treated animals showed alterations in normal hepatic histoarchitecture, which comprised of necrosis and vacuolization of the cells. However, the rats treated with Vitamin E+NDEA showed that the liver cells were normal, with very little necrosis (Day 21). This study concludes that the pre-treatment with Vitamin E prior to the administration of NDEA, reduced the degree of oxidative stress, although this vitamin produced only slight changes in the hepatic injury, in a time-dependent manner.     

Protective effects of an extract of young radish (Raphanus sativus L) cultivated with sulfur (sulfur-radish extract) and of sulforaphane on carbon tetrachloride-induced hepatotoxicity

The protective effects of an extract of young radish (Raphanus sativus L) cultivated with sulfur (sulfur-radish extract) and of sulforaphane, an isothiocyanate, on carbon tetrachloride (CCl(4))-induced liver injury were observed in mice. CCl(4) produced a marked increase in the serum level of alanine aminotransferase (ALT), primed lipid peroxidation, and resulted in intense necrosis due to oxidative stress. Oral administration of the sulfur-radish extract and of sulforaphane after CCl(4)-induced liver injury both decreased the serum level of ALT, reduced the necrotic zones, inhibited lipid peroxidation, and induced phase 2 enzymes without affecting cytochrome P450-2E1 (CYP2E1). These results suggest that the administration of the sulfur-radish extract and of sulforaphane may partially prevent CCl(4)-induced hepatotoxicity, possibly by indirectly acting as an antioxidant by improving the detoxification system.     

供体骨髓干细胞输注联合肝移植治疗终末期肝病的近期效果观察

目的评价供体骨髓干细胞输注联合肝移植治疗终末期肝病的近期效果。方法2008年3月至2009年1月本中心30例肝移植受者分为两组,实验组8例,行同期供体骨髓干细胞联合肝脏移植;对照组22例,仅行肝脏移植,不行骨髓干细胞输注。观察两组受者术后免疫抑制剂（甲基强的松龙、他克莫司）用量、肝功能（谷氨酸转氨酶、天冬氨酸转氨酶等）变化、急性排斥反应和感染并发症发生情况,以及术后住院时间和费用。采用,检验、方差分析及确切概率法进行统计学分析。结果实验组术后甲基强的松龙总用量和出院时每日他克莫司用量显著低于对照组[甲基强的松龙分别为（1314±105）mg,（1884±256）mg,t=6．060,P=0．000;他克莫司分别为（3．73±0．35）mg／d,（4．93±0．62）mg／d,,=5．147,P=0．000]。术后第1天实验组血清谷氨酸转氨酶、天冬氨酸转氨酶均显著低于对照组[谷氨酸转氨酶分别为（875．2±325．5）IU／L,（1350．4±482．7）IU／L,t=2．543,P=0．016,天冬氨酸转氨酶分别为（646．2±184．9）IU／L,（1021．8±325．4）IU／L,t=3．067,P=0．005]。术后第3天也低于对照组[谷氨酸转氨酶分别为（252．9±35．8）IU／L,（343．5±47．8）IU／L,f=4．866,P=0．000,天冬氨酸转氨酶分别为（227．8±38．0）IU／L,（310．8±61．7）IU／L,t=3．545,P=0．001]。结论同期供体骨髓干细胞联合肝脏移植可以降低术后免疫抑制剂用量,减轻术后早期肝脏损伤,不增加治疗风险,是一种安全有效的治疗方法。     

Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels

This work analyzes the prevalence of TTV DNA in peripheral blood cells from patients with hepatic alterations and healthy blood donors and measures levels of sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in certain randomly selected patients. DNA samples from 111 individuals were evaluated. They were divided into two groups, "A" (study) and "B" (control), including 54 patients with liver enzyme alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors, respectively. TTV DNA was determined by nested PCR. Certain products of the second-round PCR were sequenced. Serum biochemical assay was performed and disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the control group B. TTV prevalence was significantly higher in patients with liver disease than in healthy donors. In group A, sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were analyzed in certain randomly selected patients and no significant difference in biochemical levels (p>0.05) was found when TTV infected and noninfected individuals were compared. Knowledge related to TTV has rapidly increased, but many fundamental aspects remain unclear. This led us to question the role of TTV and doubt remains as to whether or not it is just a commensal virus. Further studies are necessary to confirm and extend these findings.