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

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

Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This study was undertaken to examine the effects of arabic gum (AG), which is commonly used in processed foods, on acetaminophen-induced hepatotoxicity in mice. Mice were given arabic gum orally (100 g l(-1)) 5 days before a hepatotoxic dose of acetaminophen (500 mg kg(-1)) intraperitoneally. Arabic gum administration dramatically reduced acetaminophen-induced hepatotoxicity as evidenced by reduced serum alanine (ALT) and aspartate aminotransferase (AST) activities. Acetaminophen-induced hepatic lipid peroxidation was reduced significantly by arabic gum pretreatment. The protection offered by arabic gum does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione, because arabic gum did not alter acetaminophen-induced hepatic glutathione depletion. Acetaminophen increased nitric oxide synthesis as measured by serum nitrate plus nitrite at 4 and 6 h after administration and arabic gum pretreatment significantly reduced their formation. In conclusion, arabic gum is effective in protecting mice against acetaminophen-induced hepatotoxicity. This protection may involve the reduction of oxidative stress.
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PMID:Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. 1452 29

Acetaminophen is used as an analgesic and antipyretic. Due to its relative safety at therapeutic dose, it is frequently used in children and in pregnant women. We evaluated the effect of a dose equivalent to the therapeutic dose of Acetaminophen in undernourished rats; 72 Wistar male rats of 18 weeks of age, with weight between 270 and 280 g, were distributed randomly in four groups: A, normal without food restriction; B, normal without food restriction treated with Acetaminophen (100 mg/kg); C; undernourished by food restriction and D, undernourished by food restriction treated with Acetaminophen (100 mg/kg). The results showed decreasing of body and hepatic weight in undernourished rats and in undernourished treated with Acetaminophen, significant decrease of serum albumin concentration (p < 0.001). It was demonstrated that activity of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase significantly decreased (p < 0.001) in the group of undernourished rats treated with Acetaminophen compared with the other groups. We concluded that the Acetaminophen induces hepatic lesions in undernourished rats treated with a single non toxic dose of 100 mg/kg of weight, probably as a consequence of the inherent susceptibility to malnutrition.
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PMID:[Modification of liver enzymes in undernourished rats treated with acetaminophen]. 1463 61

The effect of oral administration of methanolic extract of Asteracantha longifolia (AL) seeds on acetaminophen (APAP)-induced acute liver damage in rats was investigated. The activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transferase) and bilirubin level in serum and the levels of cholesterol, triglycerides, and free fatty acids in both serum and liver were found to be increased when rats were challenged with APAP. This was also associated with a significant reduction of serum and tissue phospholipids. Pretreatment with AL extract prior to the administration of APAP prevented these alterations as evidenced by liver histopathology. Results indicated that the extract could offer protection against APAP-induced liver damage, suggesting its hepatoprotective activity.
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PMID:Evaluation of the protective efficacy of Asteracantha longifolia on acetaminophen-induced liver damage in rats. 1529 74

Caffeic acid and quercetin, the well-known phenolic compounds widely present in the plant kingdom, were investigated for their possible protective effects against paracetamol and CCl4-induced hepatic damage. Paracetamol at the oral dose of 1 g/kg produced 100% mortality in mice while pretreatment of separate groups of animals with caffeic acid (6 mg/kg) and quercetin (10 mg/kg) reduced the death rate to 20% and 30%, respectively. Oral administration of sub-lethal dose of paracetamol (640 mg/kg) produced liver damage in rats as manifested by the significant (P<0.01) rise in serum levels of aminotransferases (aspartate transaminase (AST) and alanine transaminase (ALT)) compared to respective control values. The serum enzyme values were significantly (P<0.01) lowered on pretreatment of rats with either caffeic acid (6 mg/kg) or quercetin (10 mg/kg). Similarly, the hepatotoxic dose of CCl4 (1.5 ml/kg; orally) also raised significantly (P<0.05) the serum AST and ALT levels as compared to control values. The same dose of the caffeic acid and quercetin was able to prevent CCl4-induced rise in serum enzymes. Caffeic acid and quercetin also prevented the CCl4-induced prolongation in pentobarbital sleeping time confirming their hepatoprotectivity. These results indicate that caffeic acid and quercetin exhibited hepatoprotective activity possibly through multiple mechanisms.
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PMID:Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. 1533 Apr 98

The effect of taurine intake on the biliary disposition and toxicity of acetaminophen (APAP) was examined in male Golden-Syrian hamsters. Animals were provided with taurine (5 mM) in drinking water for 1 week followed by APAP treatment (250 mg/kg, i.p.). Biliary excretion and plasma concentrations of APAP and its major metabolites were determined for up to 360 min. Taurine increased the bile flow, whereas the concentration of APAP or the metabolites in bile was not altered significantly. Accordingly the total biliary excretion of APAP and the metabolites was increased in hamsters fed taurine. Taurine increased the plasma concentrations of APAP-glutathione (GSH) and APAP-mercapturate, but the APAP-glucuronide or APAP-sulfate concentration was not changed. The area under the curve of the plasma APAP concentration was reduced significantly, suggesting that the elimination of APAP was enhanced by taurine intake. However, the hepatotoxicity resulting from a dose of APAP (450 mg/kg, i.p.) was not altered by taurine intake as determined by the elevation of serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities. The results suggest that taurine administration could affect the disposition of APAP by enhancing its metabolism through the GSH-dependent pathway and also by increasing the biliary excretion of this drug and its metabolites. The pharmacological significance of this finding remains to be examined.
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PMID:Effect of taurine on biliary excretion and metabolism of acetaminophen in male hamsters. 1551 25

Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneficial effect of 2-mercaptoethane sulphonate (MESNA), an antioxidant agent, against acetaminophen toxicity in mice. Balb-c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg(-1) MESNA (MES group); a single dose of 900 mg kg(-1) i.p. acetaminophen (AA4h and AA24h groups); and MESNA, at a dose of 150 mg kg(-1) after acetaminophen injection (AA4h-MES and AA24h-MES groups). The MESNA injection was repeated once more 12 h after the first injection in the AA24h-MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically. Blood urea nitrogen and serum creatinine, which were increased significantly (P < 0.001) following acetaminophen treatment were decreased significantly (P < 0.05-0.001) after treatment with MESNA. The ALT and AST levels were also increased significantly (P < 0.001) after acetaminophen treatment but were not reduced with MESNA. Acetaminophen treatment caused a significant (P < 0.05-0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by MESNA treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with MESNA. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that MESNA, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a 'tissue injury-limiting agent' must be elucidated further in drug-induced oxidative damage.
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PMID:Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. 1566 31

Enzyme levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) increased following paracetamol induction were significantly lowered due to pretreatment with the beta-carotene (BC). This supplementation reversed the trend inducing a significant decrease in bilirubin and urea levels. Paracetamol administration significantly reduced hepatic glycogen, glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GSH-R). Pretreatment of rats with BC significantly increased the enzyme activities. The results suggest hepatoprotective activity of BC.
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PMID:Antihepatotoxic effect of beta-carotene on paracetamol induced hepatic damage in rats. 1587 20

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.
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PMID:Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver. 1615 51

In vivo protective effects of s-allyl cysteine (SAC) and s-propyl cysteine (SPC) against acetaminophen-induced hepatotoxicity in Balb/cA mice were studied. SAC and SPC at 1g/L were added into drinking water for four weeks and followed by acetaminophen treatment. Acetaminophen treatment significantly depleted glutathione content, increased oxidation stress and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P < 0.05); however, the intake of SAC or SPC significantly alleviated glutathione depletion and the elevation of ALT and AST, enhanced glutathione peroxidase activity, and lowered malondialdehyde formation (P < 0.05). Plasma levels of C-reactive protein (CRP), von Willebrand factor (vWF), IL-6, IL-10 and TNF-alpha were significantly increased by acetaminophen treatment (P < 0.05); and SAC or SPC intake significantly suppressed acetaminophen-induced elevation of CRP, vWF and the three cytokines (P < 0.05). Acetaminophen treatment also significantly increased plasminogen activator inhibitor-1 (PAI-1) activity and plasma fibrinogen level, and decreased antithrombin III (AT-III) and protein C activities (P < 0.05). SAC or SPC intake alleviated AT-III and protein C reduction (P < 0.05); but did not affect PAI-1 activity and plasma fibrinogen level (P > 0.05). These data suggest that SAC and SPC are potential multiple-protective agents against acetaminophen-induced hepatotoxicity.
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PMID:Protective effect of s-allyl cysteine and s-propyl cysteine on acetaminophen-induced hepatotoxicity in mice. 1618 16


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