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1.
Role of S-adenosyl-L-methionine in liver health and injury   总被引:10,自引:0,他引:10  
S-adenosylmethionine (SAMe) has rapidly moved from being a methyl donor to a key metabolite that regulates hepatocyte growth, death, and differentiation. Biosynthesis of SAMe occurs in all mammalian cells as the first step in methionine catabolism in a reaction catalyzed by methionine adenosyltransferase (MAT). Decreased hepatic SAMe biosynthesis is a consequence of all forms of chronic liver injury. In an animal model of chronic liver SAMe deficiency, the liver is predisposed to further injury and develops spontaneous steatohepatitis and hepatocellular carcinoma. However, impaired SAMe metabolism, which occurs in patients with mutations of glycine N-methyltransferase (GNMT), can also lead to liver injury. This suggest that hepatic SAMe level needs to be maintained within a certain range, and deficiency or excess can both lead to abnormality. SAMe treatment in experimental animal models of liver injury shows hepatoprotective properties. Meta-analyses also show it is effective in patients with cholestatic liver diseases. Recent data show that exogenous SAMe can regulate hepatocyte growth and death, independent of its role as a methyl donor. This raises the question of its mechanism of action when used pharmacologically. Indeed, many of its actions can be recapitulated by methylthioadenosine (MTA), a by-product of SAMe that is not a methyl donor. A better understanding of why liver injury occurs when SAMe homeostasis is perturbed and mechanisms of action of pharmacologic doses of SAMe are essential in defining which patients will benefit from its use.  相似文献   

2.
目的 探讨S-腺苷蛋氨酸(SAMe)对梗阻性黄疸患者肝蛋白质合成及肝功能的影响.方法 选取梗阻性黄疸患者60例,依据单双号分为观察组和对照组,各30例,两组患者均给予常规保肝治疗,在此基础上观察组加用SAMe 1 g静脉滴注,两组均治疗7d,比较治疗前后前清蛋白(PA)、清蛋白(ALB)、转铁蛋白(TF)、天冬氨酸氨基转移酶(AST)、谷氨酸氨基转移酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)、谷酰转肽酶(GGT)、碱性磷酸酶(ALP)变化.结果 观察组患者在治疗后PA较治疗前明显升高(P<0.05),治疗后浓度高于对照组(P<0.05),对照组治疗后TF较治疗前有所下降(P<0.05),治疗后浓度低于观察组(P<0.05),两组在治疗前后ALB均无明显变化(P>0.05);两组治疗后AST、ALT、TBIL、DBIL、GGT、ALP较治疗前均有所下降(P<0.05),观察组以上肝功能指标下降幅度明显较对照组高(P<0.05).结论 SAMe用于治疗梗阻性黄疸能促进患者肝蛋白质合成及改善肝功能.  相似文献   

3.
S-Adenosyl-L-methionine (SAMe) is a physiologic precursor of thiols and sulfurated compounds, which are known to be decreased in patients with liver disease. The effect of its administration on the hepatic glutathione content of liver patients was investigated. Four groups of subjects were selected: a) 9 patients with alcoholic liver disease treated with SAMe (1.2 g/day orally for 6 months); b) 7 patients with non-alcoholic liver disease treated as above; c) 8 placebo-treated patients with alcoholic liver disease; and d) 15 normal subjects as a control group. Total and oxidized glutathione were assayed by high-performance liquid chromatography of liver biopsy specimens before and after the treatment period. In all patients pre-treatment hepatic glutathione was significantly decreased as compared with controls. SAMe therapy resulted in a significant increase of hepatic glutathione levels both in patients with alcoholic and in those with non-alcoholic liver diseases as compared with placebo-treated patients. SAMe may therefore exert an important role in reversing hepatic glutathione depletion in patients with liver disease.  相似文献   

4.
The hepatic cellular damage induced by liver ischemia was investigated in rats with obstructive jaundice. Hepatic tissue blood flow in obstructive jaundice was decreased in the relation to the duration of jaundice. The value of lipid peroxide and cathepsin D activity of the hepatic tissue increased in the obstructive jaundice. Therefore, it was suggested that cell membrane and lysosomal membrane injury were induced in obstructive jaundice. The value of lipid peroxide of hepatic tissue in obstructive jaundice was more increased after partial liver ischemia. The survival rate following hepatic ischemia in jaundiced rats was remarkably lower than that of normal rats, and also it related to the duration of jaundice. In addition, histological changes of the liver after partial ischemia are severe in obstructive jaundiced liver. These data suggest that more remarkable hepatic cellular damage than in normal liver may be induced by liver ischemia in obstructive jaundice.  相似文献   

5.
It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3′,5′-cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.  相似文献   

6.
The dynamic aspects of glutathione metabolism during obstructive jaundice were analyzed in rats. Plasma bilirubin levels increased after ligation of the bile duct, with a concomitant increase in hepatorenal glutathione levels. When the bile duct was recanalized, plasma bilirubin levels rapidly decreased, with a concomitant decrease in hepatorenal glutathione levels. The half-life of hepatic glutathione turnover increased markedly after bile duct obstruction, returning to normal after recanalization of the bile duct. Intravenous administration of a loading dose of bilirubin inhibited the biliary secretion of glutathione in a dose-dependent manner. On the other hand, renal glutathione efflux increased markedly after bile duct obstruction. These observations suggest that glutathione status is significantly affected in obstructive jaundice, predominantly due to the inhibition of hepatic secretion by increased bilirubin.  相似文献   

7.
This study was undertaken to determine whether S-adenosyl-L-methionine (SAMe) changes the lipid composition and fluidity of erythrocyte membranes in chronic liver disease. SAMe was administered intravenously at a daily dose of 600 mg for 2 weeks to 10 patients; 6 patients with cirrhosis and four with primary biliary cirrhosis. The elevated free cholesterol to phospholipid molar (C/PL) ratio of the erythrocyte membranes of the patients (0.857 +/- 0.018) significantly decreased after the administration of SAMe (1 week, 0.823 +/- 0.021; 2 weeks, 0.823 +/- 0.013). In all of the four patients whose erythrocyte membrane fluidity was measured, fluidity improved with the administration of SAMe and correlated with the C/PL ratio of the membranes. These results suggest that SAMe decreases the C/PL ratio of erythrocyte membranes and thus improves membrane fluidity in chronic liver disease.  相似文献   

8.
BACKGROUND/AIMS: The mechanisms of liver injury in conditions of biliary obstruction are poorly understood. Hepatic oxidative injury has been observed in experimental models of cholestasis. Little is known in humans. This study aimed to gain more insights into the hepatic redox status in human cholestasis. METHODS: Liver concentrations of total glutathione, protein sulfhydryls and malondialdehyde (end-product of lipid peroxidation) were measured in hepatic specimens of 12 patients with obstructive jaundice before and after the application of an external biliary drainage and in six control subjects. RESULTS: Compared to control subjects, biliary obstructed patients showed significantly (P < 0.001) lower concentrations of hepatic glutathione and protein sulfhydryls, and higher (P < 0.001) levels of malondialdehyde, in the presence of comparable protein concentrations. Two-weeks after the application of external biliary drainage, cholestatic indices were significantly improved and the observed changes in glutathione, protein sulfhydryls and malondialdehyde levels, significantly decreased. CONCLUSIONS: This study shows that cholestasis is associated with a decreased protein and non-protein sulfhydryl content in the liver and with an increased lipid peroxidation. These alterations reversed almost completely after biliary drainage, indicating the cholestasis itself as the determining factor for the redox status impairment observed in the liver of patients with extra-hepatic biliary obstruction.  相似文献   

9.
BACKGROUND/AIMS: Both dilinoleoylphosphatidylcholine (DLPC) and S-adenosylmethionine (SAMe) have antioxidant properties and antifibrogenic actions. Because H2O2 mediates signal transduction-stimulating liver fibrogenesis, we investigated whether DLPC and SAMe attenuate the production of tissue inhibitor of metalloproteinase (TIMP)-1 by inhibiting H2O2 formation. METHODS: LX-2 human hepatic stellate cells were treated with leptin with or without DLPC, SAMe or various inhibitors. RESULTS: Leptin-stimulated TIMP-1 mRNA and its protein were diminished by DLPC or SAMe alone, and the response was fully prevented by the combination of DLPC and SAMe. H2O2 was increased while glutathione was decreased; these changes were prevented by AG490, suggesting a Janus kinases (JAK)-mediated process. Up-regulation of leptin receptor and activation of JAK1 and 2 were not affected by DLPC+SAMe, whereas phosphorylation of ERK1/2 and p38 was blocked by DLPC+SAMe or catalase, suggesting an H2O2-dependent mechanism. These treatments also suppressed leptin-stimulated TIMP-1 promoter activity and decreased TIMP-1 mRNA stability, contributing to TIMP-1 mRNA down-regulation. PD098059, an ERK1/2 inhibitor, suppressed TIMP-1 promoter activity, whereas SB203580, a p38 inhibitor, decreased TIMP-1 message stability; both resulted in a partial reduction of TIMP-1 mRNA. CONCLUSION: As decreased TIMP-1 production may enhance collagen deposition, the combined administration of DLPC+SAMe should be considered for the prevention of H2O2-mediated signaling and the resulting fibrosis.  相似文献   

10.
Normal differentiated hepatocytes primarily metabolize methionine, via homocysteine synthesis, through the transsulfuration pathway. In addition to glutathione, this pathway produces α-ketobutyrate that is further metabolized in the mitochondria. It is only under low methionine conditions that differentiated hepatocytes predominantly regenerate methionine from homocysteine. In contrast, proliferating hepatocytes and liver cancer cells regenerate methionine from homocysteine regardless of the availability of methionine. Here we propose that this less efficient metabolism of methionine in proliferating hepatocytes and cancer cells is an adaptation to the "Warburg effect" that is, to the well known phenomenon that cancer cells rely on aerobic glycolysis instead of oxidative phosphorylation to generate energy. The observation that knockout mice with impaired S-adenosylmethionine (SAMe) synthesis (the first step in methionine metabolism) or catabolism spontaneously develop fatty liver and hepatocellular carcinoma, together with the observation that SAMe administration induces apoptosis in hepatoma cells and prevents liver cancer support this hypothesis.  相似文献   

11.
The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and β-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein. Abstracts of this study were presented at the 28th Annual Meeting of the Japan Society of Hepatology (Tokyo, 1992), at the 20th Annual Meeting of the Japanese Society for Vascular Surgery (Sapporo, 1992), and at the 41st Annual Meeting of the Japanese Society of Gastroenterological Surgery (Kobe, 1993).  相似文献   

12.
We investigated whether S -adenosyl-L-methionine(SAMe), dilinoleoylphosphatidylcholine (DLPC), or SAMe+ DLPC influence liver lipid composition as well asacute ethanol hepatotoxicity in the isolated perfused rat liver (IPRL). SAMe (25 mg/kgintramuscularly three times a day) was administered forfive consecutive days, while DLPC was administeredintraperitoneally for five days. The liver was thenisolated, perfused with taurocholate to stabilize bilesecretion, and exposed to 0.5% ethanol for 70 min. SAMe,without changing total phospholipid (PL) content,induced an increase in the phosphatidylcholine/phosphatidylethanolamine (PC/PE) molar ratio in both liver homogenateand microsomes and a significant enrichment of 16:0-20:4and 18:0-20:4 PC molecular species. DLPC induced asignificant enrichment of PL in liver homogenate and microsomes due to a contemporary increasein PC and PE. The PC enrichment specifically involved16:0-20:4 and 18:0-20:4 PC molecular species besides theHPLC peak containing the administered 18:2- 18:2 PC species. DLPC + SAMe increased theconcentration of PC in liver homogenate and microsomesdue to a specific enrichment of 16:0-22:6, 16:0-20:4,and 18:0-20:4 PC molecular species, and the HPLC peakcontaining the administered 18:2-18:2 PC species. Ethanolacute exposure in the control IPRLs for 70 min induceda depletion of cholesterol in both liver homogenate andmicrosomes without significant changes in the composition of PL classes and PC molecularspecies. SAMe, DLPC, or SAMe + DLPC counteracted thecholesterol depletion induced by ethanol, indicatingthat phospholipid changes promoted by these treatments all induce a major resistance of livermembranes to the effect of ethanol. Ethanoladministration in control IPRLs induced a fivefoldincrease of AST and LDH release in the perfusate,depletion of glutathione in homogenates and mitochondria, decreasedoxygen liver consumption, and inhibition of bile flow.These effects of ethanol were significantly antagonizedby SAMe. In contrast, DLPC alone only minimally attenuated enzyme release in the perfusate andthe inhibitory effect of ethanol on bile flow, but itfailed to influence the depletion of total andmitochondrial glutathione or the depressed oxygenconsumption induced by ethanol. DLPC, administered togetherwith SAMe, added nothing to the protective effect ofSAMe against ethanol hepatotoxicity and cholestasis. Inconclusion, this study demonstrates that both SAMe and DLPC induced marked modifications inthe lipid composition of liver membranes with a similarenrichment of polyunsaturated PC molecular species. OnlySAMe, however, significantly protected against the hepatotoxic and cholestatic effect of acuteethanol administration, an effect associated withmaintained normal glutathione mitochondrial levels andoxygen liver consumption. This indicates that the protective effect of SAMe against ethanoltoxicity is linked to multiple mechanisms, themaintenance of glutathione levels probably being one ofthe most important.  相似文献   

13.
AIM: To examine the possible effects of honey supplementation on hepatic damage due to obstruction of the common bile duct in an experimental rat model. METHODS: The study was performed with 30 male rats divided into three groups: a sham group, an obstructive jaundice group, and an obstructive jaundice plus honey group. At the end of the study period, the animals were sacrificed, and levels of nitric oxide (NO), and NO synthase (NOS) activities were measured in liver tissues, and levels of adenosine deaminase (ADA) and alanine transaminase (ALT) activities were measured in serum.
RESULTS: Blood ALT and ADA activities were significantly elevated in the jaundice group as compared to those of the sham group. In the obstructive jaundice plus honey group, blood ALT and ADA activities were significantly decreased as compared to those of the jaundice group. In erythrocytes and liver tissues, NO levels were found to be significantly higher in the obstructive jaundice plus honey group compared to those of the sham group. Additionally, NO levels were found to be significantly higher in liver tissues from the animals in the obstructive jaundice plus honey group than those of the jaundice group.
CONCLUSION: Honey was found to be beneficial in the prevention of hepatic damage due to obstruction of the common bile duct.  相似文献   

14.
《Annals of hepatology》2013,12(2):183-189
Methionine is an essential amino acid that is metabolized mainly by the liver where it is converted to S-adenosylmethionine (SAMe) by the enzyme methionine adenosyltransferase. Although all mammalian cells synthesize SAMe, the liver is where the bulk of SAMe is generated as it is the organ where about 50% of all dietary methionine is metabolized. SAMe is mainly needed for methylation of a large variety of substrates (DNA, proteins, lipids and many other small molecules) and polyamine synthesis, so if the concentration of SAMe falls below a certain level or rises too much the normal function of the liver will be also affected. There are physiological conditions that can affect the hepatic content of SAMe. Consequently, to control these fluctuations, the rate at which the liver both synthesizes and catabolizes SAMe is tightly regulated. In mice, failure to do this can lead to fatty liver disease and to the development of hepatocellular carcinoma (HCC). Therefore, maintaining SAMe homeostasis may be a therapeutic target in nonalcoholic steatohe-patitis, alcoholic- and non-alcoholic liver cirrhosis, and for the chemoprevention of HCC formation.  相似文献   

15.
BACKGROUND/AIMS: Until now, there has been no adequate means of evaluating the liver functional reserve in cases with obstructive jaundice. 99mTC-GSA (99mTechnetium-DTPA-Galactosyl-human serum albumin) is a new liver-imaging agent which binds specifically to the asyaloglycoprotein-receptor on the membrane of hepatocytes. So, the liver imaging by GSA excludes the influence of the reticuloendothelial system. Therefore, the uptake of 99mTC-GSA is considered to be a useful method for the estimation of liver functional reserve in cases with obstructive jaundice. METHODOLOGY: In this study, we examined the uptake rate and specific binding capacities of 99mTC-GSA to receptors on the membrane of hepatocytes following 1, and 2 weeks of bile-duct ligation and 1 week after reduction of jaundice using the rat model. RESULTS: The hepatic uptake rate decreased as the period of jaundice was prolonged and returned to nearly normal by the reduction of jaundice. The value of specific binding capacities at 2 weeks after bile-duct ligation decreased significantly compared to the value of the control and the reduced group (P < 0.05). The cause of decrease in specific binding capacities was indicated as the decrease of affinity constant especially in the high affinity part. These results coincide with the change of binding capacities of insulin and glucagon receptors with obstructive jaundice, which accurately reflect the severity of hepatocyte injury. CONCLUSIONS: Taking together these results, 99mTC-GSA liver scintigraphy is thought to be a useful method to evaluate the liver functional reserve in cases with jaundice.  相似文献   

16.
Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.  相似文献   

17.
The present study aimed to investigate the roleof nitric oxide on the oxidative damage in isolatedrabbit gastric cells exposed to hypoxia-reoxygenation.Nitric oxide synthesis modulators such as L-arginine and NG-nitro-L-arginine methylester, a nitric oxide donor, sodium nitroprusside, andsuperoxide dismutase were used to treat the cells, andthe synthesis and secretion of mucus, lipid peroxideproduction, and glutathione contents of the cells weredetermined. As a result, hypoxia-reoxygenation decreasednitric oxide production and the synthesis and secretionof mucus, as well as glutathione contents of gastric cells, but hypoxia-reoxygenation increasedlipid peroxide production. Pretreatment with L-arginine,a substrate for nitric oxide synthase, sodiumnitroprusside, and superoxide dismutase prevented theincrease in lipid peroxide production and the decreasesin glutathione contents, as well as the synthesis andsecretion of mucus induced by hypoxia-reoxygenation.However, NG-nitro-L-arginine methyl ester, anitric oxide synthase inhibitor, had no effect onthese alterations. In conclusion, nitric oxide has anantioxidant defensive role on gastric cells bymaintaining mucus and glutathione.  相似文献   

18.
Aging is accompanied by changes in the morphology and physiology of organs and tissues, such as the liver. This process might be due to the accumulation of oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species (RNS). Hepatocytes are very rich in mitochondria and have a high respiratory rate, so they are exposed to large amounts of ROS and permanent oxidative stress. S-Adenosylmethionine (SAMe) is an endogenous metabolite that has shown to exert protective effects on different experimental pathological models in which free radicals are involved. The aim of this study was to investigate the effect of SAMe on age-induced damage in hepatocytes. For this purpose, male and female Wistar rats of 18 and 2 months of age were used. Cells were isolated and, after incubation in the presence or in the absence of SAMe, different parameters were measured. Aging induced a significant increase in nitric oxide, carbon monoxide and cGMP, and a reduction in reduced glutathione, ATP and phosphatidylcholine synthesis, as well as in methionine- adenosyl-transferase and methyl-transferase activities. Incubation of old cells with SAMe prevented all these age-related changes, reaching values in some of the parameters similar to those found in young animals. In conclusion, SAMe seems to have beneficial effects against age-induced damage in hepatocytes.  相似文献   

19.
The role of leukotriene (LT) on liver regeneration after hepatectomy is still unknown. LTB4 stagnates in the liver with obstructive jaundice, because LTB4 is excreted in the bile; therefore, LTB4 may have an effect on liver regeneration after hepatectomy with obstructive jaundice. Release of obstructive jaundice and simultaneous 70% hepatectomy was performed in rats to study the effect of 5-lipoxygenase inhibitor (AA-861) on liver regeneration. Group 1 underwent hepatectomy with administration of 0.1 mL dimethyl sulfoxide (DMSO), group 2 underwent hepatectomy with administration of AA-861 (20 mg/kg/d) dissolved in 0.1 mL DMSO, group 3 underwent hepatectomy with administration of AA-861 (40 mg/kg/d) dissolved in 0.1 mL DMSO, group 4 underwent release of obstructive jaundice and hepatectomy with administration of 0.1 mL DMSO, and group 5 underwent relief of obstructive jaundice and hepatectomy with administration of AA-861 (20 mg/kg/d). DMSO or AA-861 was administered 24 hours before, during, and 24 hours after hepatectomy in each group. Whole blood LTB4 and serum alanine aminotransferase (ALT), total bilirubin, and bromodeoxyuridine labeling index (LI) were measured before and after hepatectomy. The LTB4 level increased during obstructive jaundice and after hepatectomy. LTB4 and serum ALT levels were significantly lower after hepatectomy in the rats that were administered AA-861, and a significantly higher LI was observed at 24 hours after hepatectomy in rats receiving AA-861. Inhibition of 5-lipoxygenase promotes liver regeneration and decreases hepatocyte injury after hepatectomy associated with obstructive jaundice. (Hepatology 1996 Mar;23(3):544-8)  相似文献   

20.
AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).METHODS: An experimental rat model of galactosamine-induced AHF was used. An inhibitor of NO synthase, nitroarginine methyl ester, or an NO donor, arginine, were administered at various doses prior to or after the induction of AHF.RESULTS: All tested groups developed AHF. Following inhibition of the endogenous NO pathway, most liver parameters improved, regardless of the inhibitor dose before the induction of liver damage, and depending on the inhibitor dose after liver damage. Prophylactic administration of the inhibitor was more effective in improving liver function parameters than administration of the inhibitor after liver damage. An attempt to activate the endogenous NO pathway prior to the induction of liver damage did not change the observed liver function parameters. Stimulation of the endogenous NO pathway after liver damage, regardless of the NO donor dose used, improved most liver function parameters.CONCLUSION: The endogenous NO pathway plays an important role in the development of experimental galactosamine-induced AHF.  相似文献   

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