Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The deleterious effects of ethanol in senescence-accelerated prone 8 mice (SAMP8) and the protective role of nicotinamide (NAM) against ethanol-induced liver injury were examined. The mice were orally administered 2 g ethanol/kg BW and 200 mg or 500 mg NAM/kg BW three times/week for 10 weeks. Results showed that ethanol elevated activity of alanine aminotransferase (ALT) significantly. Ethanol also enhanced the formation of malondialdehyde (MDA) and protein carbonyls in the liver, whereas ethanol treatment resulted in significantly lower activity of hepatic glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD). Hematoxylin and eosin staining indicated moderate to severe fatty infiltration but not fibrosis. Administration of high NAM (500 mg/kg BW) led to markedly decreased levels of hepatic MDA, protein carbonyls, fatty infiltration and the activity of ALT, and increased activity of GPx, catalase and SOD in the ethanol-fed group. Thus, using SAMP8 as animal model for ethanol-induced liver injury in the aged mice, this study demonstrates that NAM is effective in protecting such damage.
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PMID:Beneficial effects of nicotinamide on alcohol-induced liver injury in senescence-accelerated mice. 1970 76

Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms.
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PMID:Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats. 1988 22

Chronic ethanol ingestion, achieved by feeding ethanol at a constant rate using intragastric tube feeding, alters the expression of genes in the liver. This is done by epigenetic mechanisms, which depend on the blood alcohol levels at the time of killing. However, acute bolus feeding of ethanol changes gene expression without lasting epigenetic changes. This occurs with histone 3 methylation and acetylation modifications. The gene expression response to an acute bolus of ethanol might be modified by feeding S-adenosylmethionine (SAMe), a methyl donor. In the present study, rats were given a bolus of ethanol (6 g/kg body weight (bw), SAMe (1 g/kg bw), ethanol + SAMe, or isocaloric glucose. The group of rats (n = 3) were killed at 3 and 12 h post bolus, and gene microarray analysis was performed on their liver cells. SAMe reduced the 3 h blood ethanol levels and increased the ALT levels at 3 h. Venn diagrams showed that alcohol changed the expression of 646 genes at 3 h post bolus and 586 genes at 12 h. SAMe changed the expression of 1,012 genes when fed with ethanol 3 h post ethanol bolus and 554 genes at 12 h post ethanol bolus. SAMe alone changed the expression of 1,751 genes at 3 h and 1,398 at 12 h. There were more changes in gene expression at 3 h than at 12 h post ethanol when ethanol alone was compared to the dextrose control. The same was true when SAMe was compared to SAMe + ethanol. Ethanol up regulated gene expression in most functional pathways at 3 h. However, when SAMe was fed with ethanol at 3 h, most pathways were down regulated. At 12 h, however, when ethanol was fed, the pathways were half up regulated and half down regulated. The same was true when SAMe + ethanol was fed. The expression of epigenetically important genes, such as BHMT and Foxn3, was up regulated 3 h post alcohol bolus. At 3 h, SAMe down regulated the expression of genes, such as BHMT, Mat2a, Jun, Tnfrs9, Ahcy 1, Tgfbr1 and 2, and Pcaf. At 12 h, the insulin signaling pathways were half down regulated by ethanol, which was partly prevented by SAMe. The MAPK pathway was up regulated by ethanol, but SAMe did not prevent this. In conclusion, profound changes in gene expression evolved between 3 h and 12 post ethanol bolus. SAMe down regulated these changes in gene expression at 3 h, and less so at 12 h.
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PMID:Gene expression modifications in the liver caused by binge drinking and S-adenosylmethionine feeding. The role of epigenetic changes. 1996 Feb 81

The importance of ethanol metabolism in the development of alcoholic liver disease remains controversial. The present study examined the effects of selective inhibition of the cytochrome P450 enzyme CYP2E1 compared with the inhibition of overall ethanol metabolism on the development of alcoholic steatohepatitis. Adult male Sprague-Dawley rats were fed via total enteral nutrition for 45 days with or without 10-12g/kg/d ethanol. Some groups were given 200mg/kg/d of the CYP2E1 inhibitor diallyl sulfide (DAS). Other groups were treated with 164mg/kg/d of the alcohol dehydrogenase (ADH) inhibitor 4-methylpyrazole (4-MP) and dosed at 2-3g/kg/d ethanol to maintain similar average urine ethanol concentrations. Liver pathology scores and levels of apoptosis were elevated by ethanol (P<.05) but did not differ significantly on cotreatment with DAS or 4-MP. However, liver triglycerides were lower when ethanol-fed rats were treated with DAS or 4-MP (P<.05). Serum alanine aminotransferase values were significantly lower in ethanol-fed 4-MP-treated rats indicating reduced necrosis. Hepatic oxidative stress and the endoplasmic reticulum (ER) stress marker tribbles-related protein 3 were increased after ethanol (P<.05); further increased by DAS but partly attenuated by 4-MP. Both DAS and 4-MP reversed ethanol increases in the cytokine, tumor necrosis factor-alpha (TNF-alpha), and the chemokine CXCL-2 (P<.05). However, neither inhibitors prevented ethanol suppression of interleukins IL-4 or IL-12. Moreover, neither inhibitors prevented ethanol increases in tumor growth factor-beta mRNA. Ethanol and DAS additively induced hepatic hyperplasia (P<.05). These data suggest that a significant proportion of hepatic injury after ethanol exposure is independent of alcohol metabolism. Ethanol metabolism by CYP2E1 may be linked in part to triglyceride accumulation, to induction of TNF-alpha, and to chemokine production. Ethanol metabolism by ADH may be linked in part to oxidative and ER stress and necrotic injury.
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PMID:The role of ethanol metabolism in development of alcoholic steatohepatitis in the rat. 2011 95

Sea tangle has long been used as Korean folk remedy to promote material health, and is one of the popular dietary supplement. This study was designed to evaluate the protective effect of fermented sea tangle (FST) against ethanol and carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. Sprague-Dawley rats were orally treated with FST (25, 250, 2500 mg/kg/day) with administration of ethanol (5 mL/kg) for 13 weeks and the single intraperitoneal (i.p.) dose of 50% CCl(4) (5 mL/kg/day, CCl(4) in olive oil) at 12 week, and repeated i.p. dose of 20% CCl(4) (2 mL/kg/day) for 1 week. Hepatotoxicity was evaluated by measuring the serum levels of glutamic pyruvate transaminase (GPT), gamma glutamyl transpeptidase (gamma-GT) and malondialdehyde (MDA) as well as the tissue levels of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol and CCl(4)-induced the rat liver damage, and significantly increased (p<0.05) the GPT, gamma-GT and MDA levels, and decreased the SOD, CAT and GPx levels. However, treatment with FST could decrease serum GPT, gamma-GT, and MDA levels significantly in plasma, and increase the activities of SOD, CAT, and GPx in liver tissues compared with ethanol and CCl(4)-treated group.
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PMID:Protective effect of fermented sea tangle against ethanol and carbon tetrachloride-induced hepatic damage in Sprague-Dawley rats. 2013 53

Transurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56,500 U/l, aspartate aminotransferase 32,700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid.
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PMID:Transient acute liver failure complicating transurethral resection syndrome. 2019 44

Ethanol metabolism by liver generates short lived reactive oxygen species that damage liver but also affects distal organs through unknown mechanisms. We hypothesized that dissemination of liver oxidative stress proceeds through release of biologically active oxidized lipids to the circulation. We searched for these by tandem mass spectrometry in plasma of rats fed a Lieber-DeCarli ethanol diet or in patients with established alcoholic liver inflammation, steatohepatitis. We found a severalfold increase in plasma peroxidized phosphatidylcholines, inflammatory and pro-apoptotic oxidatively truncated phospholipids, and platelet-activating factor, a remarkably potent and pleiotropic inflammatory mediator, in rats chronically ingesting ethanol. Circulating peroxidized phospholipids also increased in humans with established steatohepatitis. However, reactive oxygen species generated by liver ethanol catabolism were not directly responsible for circulating oxidized phospholipids because the delayed appearance of these lipids did not correlate with ethanol exposure, hepatic oxidative insult, nor plasma alanine transaminase marking hepatocyte damage. Rather, circulating oxidized lipids correlated with steatohepatitis and tumor necrosis factor-alpha deposition in liver. The organic osmolyte 2-aminoethylsulfonic acid (taurine), which reduces liver endoplasmic reticulum stress and inflammation, even though it is not an antioxidant, abolished liver damage and the increase in circulating oxidized phospholipids. Thus, circulating oxidized phospholipids are markers of developing steatohepatitis temporally distinct from oxidant stress associated with hepatic ethanol catabolism. Previously, circulating markers of the critical transition to pathologic steatohepatitis were unknown. Circulating oxidatively truncated phospholipids are pro-inflammatory and pro-apoptotic mediators with the potential to systemically distribute the effect of chronic ethanol exposure. Suppressing hepatic inflammation, not ethanol catabolism, reduces circulating inflammatory and apoptotic agonists.
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PMID:Chronic alcohol exposure increases circulating bioactive oxidized phospholipids. 2046 Mar 74

In traditional Chinese medicine, the flower of Pueraria lobata (Puerariae Flos) has been used in therapy to counteract the problems associated with alcohol drinking and liver injury. In this study, we investigated the hepatoprotective effects and its mechanisms of tectoridin, an isoflavone glycoside from the flower of P. lobata (Willd.) Ohwi. Ethanol (5g/kg) was given orally every 12h for a total of three doses. 1h after the last dose of ethanol, tectoridin (25, 50 and 100mg/kg) was given intragastrically five times in three consecutive days. The mice were sacrificed at 4h after tectoridin treatment. Peroxisome proliferators-activated receptor alpha (PPARalpha), sterol regulatory element-binding protein (SREBP)-1c and their target genes were evaluated by biochemical analysis and quantitative real-time polymerase chain reaction (qPCR). Mitochondria were isolated for the mitochondrial permeability transition (MPT) and membrane potential (DeltaPsi(m)) assay. Acute ethanol exposure resulted in the significant increase of the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) levels and hepatic mitochondria dysfunction shown as the increase of MPT and the decrease of DeltaPsi(m). However, tectoridin treatment dramatically attenuated these effects. In addition, tectoridin remarkably alleviated the over-production of thiobarbituric acid-reactive substance. Furthermore, tectoridin inhibited the decrease of PPARalpha expression and its target genes, including medium-chain acyl-CoA dehydrogenase (MCAD), acyl-CoA oxidase (ACO) and cytochrome P450 4A (CYP 4A) at mRNA and enzyme activity levels. These data showed that tectoridin protected against ethanol-induced liver steatosis mainly through modulating the disturbance of PPARalpha pathway and ameliorating mitochondrial function.
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PMID:Tectoridin, an isoflavone glycoside from the flower of Pueraria lobata, prevents acute ethanol-induced liver steatosis in mice. 2063 25

Flunitrazepam (FNZ) is a benzodiazepine derivative more potent than diazepam. FNZ abuse in the US has emerged in the last few years and has a growing popularity among young people and drug abusing populations. Ethanol (EtOH) consumption with FNZ enhances euphoria and onset of action. It is postulated that FNZ and EtOH cause liver cell injury. In this study, hepatocytes are employed to study the hepatotoxicity of FNZ, EtOH and their combination (FNZ-EtOH). Hepatocytes (2x10(6) cells/ml) isolated from male Sprague-Dawley rats were exposed to saline, FNZ, EtOH or FNZ-EtOH in combination. The uptake of 0.4% trypan blue and the leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes into the incubation media were used to assess cell membrane damage of hepatocytes. Where metabolism of FNZ is nearly complete through several hepatic pathways, animal pretreatment with Phenobarbital was used to study the effect of microsomal enzyme induction on cellular injury. FNZ (0.16mm), EtOH (32.56mm) or their combination caused a significant (P<0.05) decrease in cell viability. Compared with control, FNZ and FNZ-EtOH in combination caused significant AST leakage over the 2-hour incubation period. EtOH alone caused significant AST leakage after 2 hours of incubation. The leakage of ALT enzyme was significant for FNZ, EtOH and FNZ-EtOH over the 2-hour incubation period. While FNZ alone did not produce any significant enzymatic leakage in the Phenobarbital pretreated groups, the leakage of ALT and AST were significant for FNZ-EtOH in combination as early as 30 minutes of incubation. A significant depletion (P<0.05) of glutathione (GSH) was observed for EtOH and FNZ-EtOH in combination treated samples. This investigation suggests that FNZ and EtOH cause hepatotoxicity, and their combinations have an additive effect in increasing liver toxicity. Induction of microsomal enzymes revealed that FNZ is more hepatotoxic than the metabolites. And FNZ alone has no effect on GSH content.
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PMID:Hepatotoxicity of flunitrazepam and alcohol in vitro. 2065 96

The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1-3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.
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PMID:Rat strain differences in susceptibility to alcohol-induced chronic liver injury and hepatic insulin resistance. 2081 53


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