UNIPROT:P17174 - FACTA Search

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)

Methanol is oxidized in-vivo to formaldehyde and then to formate, and these processes are accompanied by the generation of free radicals. We have studied the effect of N-acetylcysteine on liver cell membrane from rats intoxicated with methanol (3.0 g kg(-1)). Evaluation of the effect was achieved by several methods. Lipid peroxidation and surface charge density were measured. An ultrastructural study of the liver cells was undertaken. The concentration of marker enzymes of liver damage (alanine aminotransferase and aspartate aminotransferase) in blood serum was measured. Methanol administration caused an increase in lipid peroxidation products (approximately 30%) as well as in surface charge density (approximately 60%). This might have resulted in the membrane liver cell damage visible under electron microscopy and a leak of alanine aminotransferase and aspartate aminotransferase into the blood (increase of approximately 70 and 50%, respectively). Ingestion of N-acetylcysteine with methanol partially prevented these methanol-induced changes. Compared with the control group, lipid peroxidation was increased by approximately 3% and surface charge density by approximately 30%. Alanine aminotransferase and aspartate aminotransferase activity increased by 9 and 8%, respectively, compared with the control group. The results suggested that N-acetylcysteine was an effective antioxidant in methanol intoxication. It may have efficacy in protecting free radical damage to liver cells following methanol intoxication.
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PMID:Protective effect of N-acetylcysteine on rat liver cell membrane during methanol intoxication. 1086 43

Exposure of human plasma in vitro to gas-phase cigarette smoke (CS) causes a marked modification of plasma proteins as measured by protein carbonyl assay. Aldehydes present in CS may cause this elevation of protein carbonyls by reacting with sulfhydryl groups of proteins. Saliva is the first body fluid to confront the inhaled CS. Thus, in vitro exposure of saliva to nine "puffs" of CS also showed a distinct increase in protein carbonyls. Ascorbate and desferrioxamine mesylate had little effect on protein carbonyl formation, while GSH and N-acetylcysteine considerably inhibited the accumulation of protein carbonyls due to CS exposure. Following the exposure to CS, the activities of several salivary enzymes-amylase, lactic dehydrogenase (LDH), and acid phosphatase-were found to be significantly reduced (34, 57, and 77%, respectively). However, CS had no effect on the activities of aspartate aminotransferase and alkaline phosphatase. Addition of 1 mM of GSH and N-acetylcysteine considerably protected LDH and amylase activities, suggesting that sulfhydryl groups are affected in LDH and amylase. On the other hand, addition of 1 mM ascorbate caused a further loss of LDH and amylase activities, which could be partially prevented by the addition of desferrioxamine mesylate, implicating metal-catalyzed oxidation processes. Finally, loss of acid phosphatase activity was completely unaffected by any of the above antioxidants. It is concluded that the loss of salivary enzyme activities may be due to various agents in the CS that affect the enzyme activities via different mechanisms.
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PMID:Effect of cigarette smoke on salivary proteins and enzyme activities. 1089 39

Acetaminophen is a widely used nonprescription analgesic and antipyretic agent. It is also a dose-related hepatotoxin that can cause fulminant liver failure when taken in massive overdoses or, much less commonly, at therapeutic doses in susceptible individuals. Persons who regularly consume alcohol or persons who have been fasting may be more susceptible to this hepatotoxicity. This liver injury is due not to the drug itself but to the formation of the toxic metabolite N-acetyl-p-benzoquinine imine generated through the cytochrome P-450 drug-metabolizing system. Normally, hepatic stores of glutathione combine with the toxic metabolite and prevent liver cell injury. When glutathione stores are depleted by overproduction of this metabolite, however, the reactive metabolite binds to liver cell proteins and causes hepatic necrosis. P-450 2E1 is induced by alcohol consumption and possibly starvation, and glutathione depletion can occur due to the inadequate nutrition occurring in chronic alcohol use or in starvation. Recent studies have shown that activated Kupffer cells and their secreted toxic agents such as cytokines may also play a role in this liver injury. This liver injury is characterized by extremely high levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (> 1000), and bad prognostic signs include severe prolongation of the prothrombin time, renal dysfunction, and, most importantly, acidosis. N-acetylcysteine is a highly effective antidote when given early (within 15 hours) of overdose. Some patients may develop such fulminant liver injury that they require transplantation. Unfortunately, many such patients have a course so rapid that a donor liver may not become available in time. Thus, both the medical community and the general public require a heightened understanding of this clinical problem in order to initiate prevention measures and to implement early therapeutic measures if an overdose situation occurs.
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PMID:Acetaminophen hepatotoxicity: An update. 1098 Sep 26

The present study was undertaken to evaluate the potential role of curcumin, the antioxidant principal from Curcuma longa Linn., and the sulphur-containing amino acid N-acetylcysteine against ethanol-induced changes in the levels of prostanoids. Biochemical assessment of liver damage was done by measuring the activities of serum enzymes (i.e., aspartate transaminase and alkaline phosphatase), which were significantly increased in rats fed ethanol, whereas the elevated levels of these enzymes were decreased after curcumin and N-acetylcysteine treatment to rats fed ethanol. We observed a significant increase in the levels of prostaglandins E(1), E(2), F(2alpha), and D(2) in liver, kidney, and brain. Administration of curcumin and N-acetylcysteine was shown to decrease the level of these prostanoids in the tissue studied.
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PMID:Changes in the prostaglandin levels in alcohol toxicity: effect of curcumin and N-acetylcysteine. 1112 Apr 49

Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/day, 3 times/wk for 4 to 8 wk. Creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum (hemisphere and vermis) and largest in the brainstem (hypothalamus, midbrain, and medulla oblongata). The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose (290 to 495 ppm) or on prolonging exposure period (4 to 8 wk). Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.
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PMID:Inhibition of creatine kinase activity in rat brain by methyl bromide gas. 1149 99

Biochemical assessment of liver damage during ethanol-induced stress was done by measuring the activities of serum enzymes, viz., aspartate transaminase (AST) and alkaline phosphatase (ALP), which were significantly elevated in rats fed ethanol. Ethanol administration for a period of 60 days modifies the fatty acid composition, and the analysis of fatty acids showed that there was a significant increase in the concentrations of palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1) in liver, kidney, and brain, whereas the concentrations of palmitoleic (16:1) and arachidonic acid (20:4) were significantly decreased. The breakdown products of arachidonic acids (20:4), prostaglandins, were elevated. The antioxidants curcumin and N-acetylcysteine (NAC) decreased the activities of serum AST and ALP. Curcumin and NAC decreased the concentrations of fatty acids, viz., palmitic, stearic, and oleic acid, whereas arachidonic acid and palmitoleic acid were elevated. The prostaglandin concentrations were also decreased after curcumin and N-acetylcysteine treatment. Thus the present investigation shows that curcumin and N-acetylcysteine prevent the fatty acid changes produced by ethanol and also reduce the inflammatory response of ethanol by reducing the level of prostaglandins.
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PMID:Potential role of antioxidants during ethanol-induced changes in the fatty acid composition and arachidonic acid metabolites in male Wistar rats. 1150 46

Cocaine produces hepatotoxicity by a mechanism that remains undefined but has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, and exposure to noninjurious doses of LPS increases the toxicity of certain hepatotoxins. Previously it was demonstrated that exposure to noninjurious doses of LPS dramatically increases cocaine-mediated hepatotoxicity (CMH). This study was conducted to investigate whether pretreatment with N-acetylcysteine (NAC), a glutathione (GSH) precursor and an antioxidant agent, inhibits LPS potentiation of CMH. For 5 consecutive days, male CF-1 mice were administered daily oral NAC (200 mg/kg) or sterile saline followed an hour later by cocaine (20 mg/kg) or sterile saline. Four hours following the last cocaine or saline treatment, the mice were administered 12 x 10(6) EU LPS/kg or sterile saline. For the cocaine alone and cocaine and LPS groups, NAC pretreatment significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities with absence of necrotic hepatic lesions, indicating a reduction of liver injury. In addition, in all groups pretreated with NAC, hepatic GSH concentration was significantly increased, as were hepatic and blood glutathione peroxidase (GPx) and catalase (CAT) activities. In conclusion, the results demonstrate that NAC pretreatment exerted a protective effect against LPS potentia-tion of CMH.
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PMID:N-acetylcysteine pretreatment decreases cocaine and endotoxin-induced hepatotoxicity. 1252 69

Acetaminophen (AA) is a commonly used analgesic and antipyretic drug; however, when used in high doses, it causes fulminant hepatic necrosis and nephrotoxic effects in both humans and experimental animals. It has been reported that the toxic effects of AA are the result of oxidative reactions that take place during its metabolism. In this study we investigated if melatonin, vitamin E or N-acetylcysteine (NAC) are protective against AA toxicity in mice. The doses of the antioxidants used were as follows: melatonin (10 mg/kg), vitamin E (30 mg/kg) and NAC (150 mg/kg). Blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in blood, and glutathione (GSH), malondialdehyde (MDA), oxidized protein levels and myeloperoxidase (MPO) activity in liver and kidney tissues were measured. BUN and serum creatinine, ALT and AST levels which were increased significantly following AA treatment decreased significantly after pretreatment with either vitamin E, melatonin or NAC; however, they were not reduced to control levels. ALT and AST levels were significantly higher at 4 hr compared with the 24 hr levels after AA administration. However, BUN and creatinine levels were significantly elevated only at 24 hr. GSH levels were reduced while MDA, MPO and oxidized protein levels were increased significantly following AA administration. These changes were reversed by pretreatment with either melatonin, vitamin E or NAC. Liver toxicity was higher at 4 hr, whereas nephrotoxicity appeared to be more severe 24 hr after treatment with AA. Vitamin E was the least efficient agent in reversing AA toxicity while melatonin, considering it was given as at lower dose than either vitamin E or NAC, was the most effective. This may be the result of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes.
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PMID:Protective effects of melatonin, vitamin E and N-acetylcysteine against acetaminophen toxicity in mice: a comparative study. 1282 15

The relationship between acetaminophen (APAP) reactive metabolite formation, nitrotyrosine (NT) production, and cytokine elevation in APAP toxicity was investigated. Mice were dosed with 300 mg/kg of APAP and sacrificed at 1, 2, 4, 8, and 12 h. Serum aspartate aminotransferase (AST) was elevated by 4 h. The relative amount of NT correlated with toxicity and was localized in the necrotic cells. IL-1b was increased at 1 h, whereas IL-6, MIP-2, and MCP-1 were increased by 4-8 h. To determine the importance of reversible versus toxic events, N-acetylcysteine (NAC) was administered to mice either before APAP or 1, 2, or 4 h after APAP. The animals were sacrificed at 12 h. NAC treatment before APAP resulted in serum AST, serum nitrate plus nitrite as a measure of nitric oxide (NO) production, and hepatic cytokine levels that were similar to the controls. No APAP protein adducts or NT was present in these animals. In mice treated with NAC at 1 h, cytokines and serum AST were normal at 12 h, but APAP protein adducts were present in the hepatic centrilobular areas. No NT was present in these animals. In mice treated with NAC at 2 h and sacrificed at 12 h, serum AST was reduced by 80%. APAP adducts and NT were present in the centrilobular areas. Mice receiving NAC at 4 h had no protection from toxicity and serum nitrate plus nitrite. The NT and cytokine levels were similar to those of mice receiving APAP alone. The data suggest a relationship between metabolic events in APAP toxicity and the upregulation of NO, and IL-1b. IL-6, MIP-2, and MCP-1 appear to follow the toxicity. While it is a pre-requisite event, covalent binding per se does not appear to be a toxic event in the development of toxicity.
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PMID:Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation. 1288 92

In the search of hepatoprotective agents from natural sources, alpha- and beta-amyrin, a triterpene mixture isolated from the trunk wood resin of folk medicinal plant, Protium heptaphyllum was tested against acetaminophen-induced liver injury in mice. Liver injury was analysed by quantifying the serum enzyme activities and by histopathological observations. In mice, acetaminophen (500 mg/kg, p.o.) caused fulminant liver damage characterized by centrilobular necrosis with inflammatory cell infiltration, an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, a decrease in hepatic glutathione (GSH) and 50% mortality. Pretreatment with alpha- and beta-amyrin (50 and 100 mg/kg, i.p. at 48, 24, and 2 h before acetaminophen) attenuated the acetaminophen-induced acute increase in serum ALT and AST activities, replenished the depleted hepatic GSH, and considerably reduced the histopathological alterations in a manner similar to N-acetylcysteine, a sulfhydryls donor. Also, the acetaminophen-associated mortality was completely suppressed by terpenoid pretreatment. Further, alpha- and beta-amyrin could potentiate the pentobarbital (50 mg/kg, i.p.) sleeping time, suggesting the possible suppression of liver cytochrome-P450. These findings indicate the hepatoprotective potential of alpha- and beta-amyrin against toxic liver injury and suggest that the diminution in oxidative stress and toxic metabolite formation as likely mechanisms involved in its hepatoprotection. In conclusion, this study supports the traditional use of Protium heptaphyllum resin as a medicinal agent and suggests the feasibility of developing herbal drugs for treatment of liver disorders.
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PMID:Protective effect of alpha- and beta-amyrin, a triterpene mixture from Protium heptaphyllum (Aubl.) March. trunk wood resin, against acetaminophen-induced liver injury in mice. 1576 70

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