Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione is important in cellular defense against oxidative stress. We postulated that administration of N-acetylcysteine (NAC), a glutathione precursor, might help maintain or replenish hepatic glutathione stores, thereby reducing reperfusion injury in liver grafts after warm ischemia. Eighteen pigs were subjected to 2 hr of warm hepatic ischemia and divided into a control group (group A, n = 6), a preischemia treatment group (group B, n = 6: NAC, 150 mg/kg, continuous i.v. infusion 1 hr before ischemia), and a postischemia treatment group (group C, n = 6: NAC, 150 mg/kg continuous i.v., begun 20 min before reperfusion and continued for 1 hr). At initiation of laparotomy, we measured hepatic levels of reduced glutathione (GSH), its oxidized form (GSSG), ATP, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Before reperfusion, after 2 hr of warm ischemia, GSH, GSSG, and ATP were measured. One hour after reperfusion, we measured GSH, GSSG, ATP, AST, and LDH. Bile output was recorded every 10 min. Postoperfusion AST and LDH were significantly lower in both treatment groups than in controls. In group B, hepatic glutathione was maintained at significantly higher levels than in controls, even after ischemia (P < 0.05). In group C, although hepatic GSH levels fell until reperfusion, after administration of NAC, hepatic GSH reached the level of the preischemia treatment group. In both treatment groups, GSH 1 hr after reperfusion was significantly higher than in the controls (P < 0.01): regeneration of glutathione was seen in all 6 animals in group C, compared with 2/6 in group B and none in the control group. ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.
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PMID:N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. 856 May 64

The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.
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PMID:Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock. 961 80

Age-associated changes in liver injury and post-necrotic regeneration were studied in rats aged 6 and 30 months in a period of 96 h following a dose of thioacetamide (6.6 mmol/kg body weight). Hepatocellular necrosis was detected in both groups by serum aspartate aminotransferase, but the severity of injury was significantly lower (one fourth, p < 0.001) in the oldest. Differences were observed in hepatocyte FAD monooxygenase activity between 6 and 30 months old rats at 24 h (278 versus 170%, p < 0.001, respectively) and also in GSH/GSSG ratio, in protein thiol groups and in malondialdehyde. Glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase activities rose markedly in both groups, this increase being slightly lower in the oldest. Superoxide dismutase and catalase did not show significant changes between both groups. At the end of the 96 h experimental period the restoration towards normal of GSG/GSSG, protein thiols malondialdehyde and the activities of Cu-Zn superoxide dismutase and catalase were significantly lower in hepatocytes from 30 months old rats. We summarize that the main age-related changes in the sequenced process of liver injury and regeneration occurred to a lesser extent in severity of injury and delayed response in the post-necrotic restoration of liver function, probably due to a lower increase in antioxidant enzyme system.
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PMID:Aging delays the post-necrotic restoration of liver function. 969 17

Effects of a single dose of betaine on the chloroform-induced hepatotoxicity were examined in adult male ICR mice. Administration of betaine (1000 mg/kg, ip) 1 to 7 hr prior to a chloroform challenge (0.25 ml/kg, ip) resulted in remarkable enhancement of hepatotoxicity as indicated by increases in serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. The potentiation of hepatotoxicity was most significant when mice were treated with betaine 4 hr earlier than chloroform. However, a 24 hr prior administration of betaine protected the animals from induction of the chloroform hepatotoxicity. Thus, its effect appeared to be highly dependent on the time lapse from the betaine pretreatment to the challenge of mice with chloroform. Betaine treated either 4 or 24 hr prior to sacrifice did not alter the hepatic contents of cytochrome P-450, cytochrome b5, or NADPH cytochrome P-450 reductase activity. Accordingly the hepatic microsomal p-nitroanisole O-demethylase, aminopyrine N-demethylase, or p-nitrophenol hydroxylase activities were not influenced by the betaine pretreatment. Betaine was shown not to affect any of the enzyme activities associated with glutathione (GSH) conjugation reaction, such as glutathione S-transferases (GSTs), glutathione disulfide (GSSG) reductase and GSH peroxidase irrespective of the time of its administration. When betaine was administered to mice 2-6 hr prior to sacrifice, hepatic GSH level, but not plasma GSH, was decreased significantly. Enhancement of the chloroform hepatotoxicity by betaine correlated well with the reduction in hepatic GSH levels. Both hepatic and plasma GSH levels were elevated in mice 24 hr following the betaine treatment. The results suggest that betaine affects induction of the chloroform hepatotoxicity by modulating the availability of hepatic GSH, which appears to be associated with its role in the transsulfuration pathway in the liver.
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PMID:Effects of singly administered betaine on hepatotoxicity of chloroform in mice. 973 16

L-2-oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. Here, its effect on alcohol-induced liver injury in an enteral alcohol feeding model was investigated. Male Wistar rats were given control high-fat or ethanol containing diets enterally for 4 weeks. Treated rats received 500 mg/kg/d of dietary OTC. Ethanol delivery, weight gain, and the cyclic pattern of ethanol in the urine were not different between the OTC-ethanol and ethanol groups. After 4 weeks, serum aspartate transaminase (AST), necrosis and inflammation were elevated significantly by ethanol compared with appropriate high-fat controls, effects blocked by OTC. Moreover, ethanol elevated hepatic tumor necrosis factor alpha (TNF-alpha) messenger RNA (mRNA) and the nuclear transcription factor nuclear factor kappaB (NFkappaB) 2-3 fold. NFkappaB in isolated Kupffer cells was also increased by ethanol. These effects were all blocked by OTC treatment. Additionally, superoxide production was higher in Kupffer cells isolated from ethanol-treated rats, an effect blunted by OTC. OTC also increased circulating glutathione (GSH) levels about 2-fold; however, GSH levels were not affected by ethanol or OTC in livers from the groups studied. Surprisingly, GSH was elevated by ethanol and OTC treatment in isolated Kupffer cells about 2-fold. Moreover, GSH (Ki-10 micromol/L) and cysteinyl-glycine, but not oxidized glutathione (GSSG) or OTC, blunted the LPS-induced increase in calcium in isolated Kupffer cells, possibly by activating a glycine-gated chloride channel due to their structural similarity with glycine. Collectively, it is concluded that GSH is protective, in part, by increasing circulating GSH, which blunts activation of Kupffer cells via the glycine-gated chloride channel.
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PMID:The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat. 1065 62

The protective effect of N-[(3, 5-di-tertiobutyl-4-hydroxy-1-thiophenyl)]-3-propyl-N'-(2,3, 4-trimethoxybenzyl)piperazine (S-15176) on liver injury induced by warm ischemia-reperfusion was investigated using a rat model. Animals were subjected to 2 h of ischemia followed by different reperfusion times. Hepatocyte integrity was assessed by measuring plasma alanine and aspartate aminotransferase activities, and by determining reduced and oxidized glutathione in plasma and bile. Hepatocyte function was quantitated by determining bile flow and liver ATP content. Ischemia-reperfusion resulted in severe hepatic injury involving a huge increase in alanine and aspartate aminotransferase activities, a drop in ATP content, and a decrease in bile flow. Plasma and bile reduced (GSH) and oxidized (GSSG) glutathione concentrations were inversely related: plasma levels increased when biliary levels decreased. This was associated with a decrease in animal survival (-34%). S-15176 pretreatment (1.25, 2.5, 5 or 10 mg kg(-1) day(-1)) improved the survival rate and limited tissue damages in a dose-dependent manner. The pretreatment also reduced the aminotransferase leakage from hepatocytes and the increase in plasma glutathione levels. In addition, normalization of the plasma GSSG/GSH ratio, a good index of an oxidative stress, was observed in groups treated with the higher dosage, suggesting that the antioxidant properties demonstrated for the compound in vitro (IC(50)=0.3 microM towards lipid peroxidation) could play a role in its protective effect. S-15176 pretreatment also protected the organ from the drop in ATP levels. At the higher dose, ATP content was maintained at a level almost 86% of the sham-operated group after 60 min of reperfusion. This was associated with a restoration of the biliary flow. These data suggest that S-15176 may be a useful drug in liver surgery to prevent ischemia-reperfusion injury.
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PMID:S-15176 reduces the hepatic injury in rats subjected to experimental ischemia and reperfusion. 1102 Apr 92

The protective effects and the possible mechanisms of dry matter of fermented filtrate (DMF) from Antrodia camphorata in submerged culture (ACSC) on H(2)O(2)-induced cytotoxicity in HepG2 and carbon tetrachloride (CCl(4))-induced hepatotoxicity in Sprague-Dawley rats were investigated. The results showed that the inhibitory effect of DMF and its crude triterpenoids on lipid peroxidation occurred in a dose-response manner in an AAPH/linoleic acid system. When HepG2 cells were pretreated with DMF at the concentration of 0.10 mg/mL for 4 h and then induced by 1 h of treatment with H(2)O(2) (100 microM), lipid peroxidation was significantly (p < 0.05) decreased, as measured by the formation of malondialdehyde. The oral pretreatment with DMF [0.25 and 0.50 mg/kg of body weight (bw)] for 5 consecutive days prior to the administration of a single dose of 40% CCl(4) (0.10 mL/100 g of bw, ip) significantly prevented the increase in serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and liver lipid peroxidation (p < 0.05). Histopathological evaluation of the rat liver revealed that DMF reduced the incidence of liver lesions, including neutrophil infiltration, hydropic swelling, and necrosis induced by CCl(4) in rats. Moreover, reduced glutathione (GSH)-dependent enzymes (glutathione peroxidase, glutathione reductase, and glutathione S-transferase) and the GSH/GSSG ratio were significantly improved in the oral pretreatment DMF of rats (p < 0.01). The results suggest that DMF may play a role in preventing oxidative damage in living systems by up-regulating hepatic GSH-dependent enzymes to preserve the normal GSH/GSSH ratio and scavenging free radicals formed during CCl(4) metabolism.
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PMID:Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats. 1261 86

The reticulocytes and the ageing red blood cells (RBCs) namely young (Y), middle-aged (M) and old RBCs (O) of female Wistar rats from different groups such as control animals (C), controls treated with vanadate (C + V), alloxan-induced diabetic (D), diabetic-treated with insulin (D + I) and vanadate (D + V), were fractionated on a percoll/BSA gradient. The following enzymes were measured - hexokinase (HK), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione-s-transferase (GST), alanine aminotransferase (AlaAT), aspartate aminotransferase (AsAT) and arginase in the hemolysates of all the RBCs fractions. Decreases in the activity of HK and AsAT by about 70%, arginase and GSH-Px by 30% in old RBCs were observed in comparison to reticulocytes of control animals. Increases in the activity of GSSG-R by 86%, AlaAT by more than 400% and GST by 70% were observed in old RBCs in comparison to reticulocytes of control animals. Alloxan diabetic animals showed a further decrease in the activities of HK in Y RBCs by 37%, M RBCs by 39% and O RBCs by 32%, GSH-Px activity in Y RBCs by 13%, M RBCs by 20% and O RBCs by 33% and GST activity in Y RBCs by 14%, M RBCs by 42% and O RBCs by 60% in comparison to their corresponding cells of control animals. An increase in the activity of all the enzymes studied was also observed in reticulocytes of diabetic animals in comparison to reticulocytes of controls. The GSSG-R activity was found to be increased in Y RBCs by 49%, M RBCs by 67% and O RBCs by 64% as compared to the corresponding age-matched cells of control animals. The activity of arginase also decreased in Y RBCs by about10%, M RBCs by 20% and O RBCs by 30% in comparison to the age-matched cells of control animals. A decrease in the activity of AsAT in Y and M RBCs by 30%, and O RBCs by 25% was observed in diabetic animals in comparison to the age-matched cells of control animals. The activity of AlaAT was found to be decreased by more than 10% in Y and M RBCs and 25% in O RBCs of diabetic animals in comparison to the age-matched cells of control animals. Insulin administration to diabetic animals reversed the altered enzyme activity to control values. Vanadate treatment also reversed the enzyme levels except for that of GST in old cells.
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PMID:Protective effects of sodium orthovanadate in diabetic reticulocytes and ageing red blood cells of Wistar rats. 1528 6

Concomitant oral supplementation of Aloe vera, (1, 2 or 5% w[sol ]v in drinking water) during arsenic exposure (0.2 mg[sol ]kg, intraperitoneally, once daily for 3 weeks) was investigated in rats for its protective value. Animals exposed to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) level in blood. White blood corpuscles (WBC) level decreased while most of the other clinical blood parameters like red blood cells count, haemoglobin, MCV, MCH, MCHC ratio and platelet number, etc. remained unaltered on arsenic exposure. Hepatic reduced GSH, oxidized glutathione (GSSG) level remained unaltered, thiobarbituric acid reactive substance (TBARS) level increased significantly while the activity of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and catalase decreased on arsenic exposure. Renal GSH contents decreased while superoxide dismutase (SOD) activity decreased significantly on arsenic exposure. Concomitant administration of Aloe vera had remarkable protective action on inhibited blood ALAD activity and restored blood GSH level while most of the other blood biochemical parameters remained unchanged on Aloe vera supplementation. Interestingly, most of hepatic biochemical variables indicative of oxidative stress showed protection; no effect of Aloe vera on blood and liver arsenic concentration was noted. Also, no effect of Aloe vera on most of the altered renal biochemical parameters were noticed. The results thus lead us to conclude that simultaneous supplementation of Aloe vera protects against arsenic induced oxidative stress but does not influence the arsenic concentration in these organs.
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PMID:Protective value of Aloe vera against some toxic effects of arsenic in rats. 1579 4

The aim of this paper is to assess the antioxidant properties of rat liver in the course of acute and chronic fasciolosis. Wistar rats were infected per os with 30 metacercariae of Fasciola hepatica. Liver activities of antioxidant enzymes and concentrations of non-enzymatic antioxidants were determined at 4, 7, and 10 weeks post-infection. Activities of superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) were decreased, catalase (CAT) activity was increased and non-enzymatic antioxidant concentrations (reduced glutathione, vitamins C, E and A) were reduced simultaneously with enhancement of lipid peroxidation processes as evidenced by increased levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Changes in the antioxidant abilities of the liver and in the phospholipid structure of the cell membrane were accompanied by rising activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of liver damage.
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PMID:Antioxidant potential of rat liver in experimental infection with Fasciola hepatica. 1592 4


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