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

---

Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paracetamol has properties that make it useful in many kinds of drugs that are readily available to users. These drugs are often used for extensive periods of time without a doctor's supervision, which might lead to unexpected overdose. The aim of this work was to assess the extent of liver damage in rabbits after administering them with paracetamol for approximately 2 months. The results we obtained suggest that paracetamol administered for a long time causes liver function impairment. It was, however, not possible to determine the impairment by measuring the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gamma-glutamylotranspeptidase (GGTP). It was determined by measuring the concentration of ketone bodies and arterial ketone body ratio (AKBR) value. Even when taken in small doses, paracetamol causes changes in liver metabolism when taken for an extended period of time.
...
PMID:The influence of small doses of paracetamol on rabbit liver. 1760 12

Dichloromethane (DCM) is metabolically converted to carbon monoxide mostly by CYP2E1 in liver, resulting in elevation of blood carboxyhemoglobin (COHb) levels. We investigated the effects of a subtoxic dose of acetaminophen (APAP) on the metabolic elimination of DCM and COHb elevation in adult female rats. APAP, at 500 mg/kg i.p., was not hepatotoxic as measured by a lack of change in serum aspartate aminotransferase, alanine aminotransferase, and sorbitol dehydrogenase activities. In rats pretreated with APAP at this dose, the COHb elevation resulting from administration of DCM (3 mmol/kg i.p.) was enhanced significantly. Also blood DCM levels were reduced, and its disappearance from blood appeared to be increased. Hepatic CYP2E1-mediated activities measured with chlorzoxazone, p-nitrophenol, and p-nitroanisole as substrates were all induced markedly in microsomes of rats treated with APAP. Aminopyrine N-demethylase activity was also increased slightly, but significantly. Western blot analysis showed that APAP treatment induced the expression of CYP2E1 and CYP3A proteins. Neither hepatic glutathione contents nor glutathione S-transferase activity was changed by the dose of APAP used. The results indicate that, contrary to the well known hepatotoxic effects of this drug at large doses, a subtoxic dose of APAP may induce CYP2E1, and to a lesser degree, CYP3A expression. This is the first report that APAP can increase cytochrome P450 (P450)-mediated hepatic metabolism and the resulting toxicity of a xenobiotic in the whole animal. The pharmacological/toxicological significance of induction of P450s by a subtoxic dose of APAP is discussed.
...
PMID:Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. 1762 Mar 48

Previous studies have suggested that patients receiving both activated charcoal (AC) and N-acetylcysteine (NAC) after acute acetaminophen (APAP) overdoses may have improved outcomes. We evaluated all acute acetaminophen overdoses that received NAC therapy reported to US poison centers for the years 1993 through 2004. Groups were separated based on therapy received: 1) both AC and NAC and 2) NAC alone. There were 97,960 acetaminophen overdoses reported, with 49,427 patients (50%) receiving NAC and AC. Reports of AST/ALT > 1000, a major effect, and death were 1301 (2.9%), 2957 (6.6%), and 232 (0.5%), respectively, for patients receiving NAC plus AC, vs. 5273 (12%), 4534 (10.3%), and 369 (0.8%), respectively, for patients receiving NAC alone (p < 0.01). Use of Toxic Exposure Surveillance System data in the present study has a number of limitations, including its retrospective nature and no documentation of when NAC therapy was initiated. It is possible that those patients who did not receive AC presented to the Emergency Department later in their overdose and had NAC therapy initiated later, and therefore they were predisposed to a greater risk of hepatic injury. Evaluation of 12 years of acute APAP overdoses suggests that the use of AC, in addition to NAC therapy, may provide improved patient outcomes.
...
PMID:Impact of activated charcoal after acute acetaminophen overdoses treated with N-acetylcysteine. 1769 65

Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including hepatotoxicity. The present study has been conducted to evaluate the eventual role of the platelet activating factor in post-acetaminophen intoxication of liver, using ginkgolide B, BN52021, a selective PAF receptor antagonist. One group of rats was treated with a toxic dose of acetaminophen (APAP) (3.5 g/kg b.w.) (control group) and a second one with the same dose of APAP followed by a dose of ginkgolide B, BN52021 (10 mg/kg b.w.) (BN52021-treated group). The animals were killed at 8, 16, 24, 32 and 40 h after treatment. APAP was found to cause an acute hepatic injury, evident by alterations of biochemical (serum enzymes: ALT, AST and ALP) and liver histopathological (degree of inflammation and apoptosis) indices, which was followed by liver regeneration evident by three independent indices ([3H] thymidine incorporation into hepatic DNA, liver thymidine kinase activity and hepatocyte mitotic index). Hepatic levels of malondialdehyde and serum cholesterol/HDL cholesterol fraction were also measured as parameters of oxidant-antioxidant balance. The protected effects of ginkgolide B were qualified during post treatment time by: (1) reduction of oxidative stress, (2) high decrease of hepatic injury, and (3) decrease of regenerating activity. These results indicate that PAF may play an important role in APAP-induced liver injury and regeneration, and that the use of ginkgolide B attenuates liver damage providing important means of improving liver function following acetaminophen intoxication.
...
PMID:Platelet activating factor (PAF) antagonism with ginkgolide B protects the liver against acute injury. importance of controlling the receptor of PAF. 1793 19

Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of hepatotoxicity of PCM. This work therefore seeks to induce liver damage in mice using single dose (25 0mg/kg) of acetaminophen and to evaluate the possible protective effects of administration (100mg/kg) of some medicinal plants (Kigelia africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) on PCM-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. Equally, comparative effects of these plants on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), gluthathione peroxidase (GPx), and delta-aminolevulinate dehydratase (delta-ALA-D) activities, were also evaluated in the mouse liver homogenate. Paracetamol caused liver damage as evident by statistically significant (P<0.05) increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, GPx, CAT, and delta-ALA-D and an increase in TBARS in the liver of paracetamol-treated group compared with the control group. However, all the tested plants except Calotropis procera were able to counteract these effects. The present results suggest that these plants can act as hepatoprotectives against paracetamol toxicity and that the mechanism by which they do this is by acting as antioxidants.
...
PMID:Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. 1805 72

Acetaminophen (APAP) overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of sesame oil on APAP-induced acute liver injury. Male Wistar rats were given APAP (1,000 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased aspartate transaminase, alanine transaminase, lipid peroxidation, and superoxide anion and hydroxyl radical generation levels; it also induced glutathione depletion. Sesame oil (8 mL/kg; orally) did not alter the gastric absorption of APAP, but it inhibited all the parameters altered by APAP and protected the rats against APAP-induced acute liver injury. We hypothesize that sesame oil maintained the intracellular glutathione levels, reduced reactive oxygen species levels, and inhibited lipid peroxidation in rats with APAP-induced acute liver injury.
...
PMID:Effect of sesame oil against acetaminophen-induced acute oxidative hepatic damage in rats. 1809 69

The hepatoprotective efficacy of irradiated hyaluronic acid (HA) on acetaminophen (APAP) induced acute hepatotoxicity was investigated. BALB/c mice (4-6 weeks of age) were pretreated with unirradiated HA (UIHA), 5 and 50 kGy gamma irradiated HA (GIHA) for 14 days and were dosed APAP (500 mg/kg b.wt). After 9h of APAP dosing animals were euthanized. The degree of acute hepatotoxicity was measured by aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The expression of interferon-gamma (IFN-gamma) in serum and alpha-and mu-class of gluthathione-S-transferase (GSTs), CYP 2E1 class of cytochrome monooxygenase and glutathione (GSH) in liver were quantified. Histological evaluation was done by Hematoxiylin and Eiosin staining, Periodic acid schiffs staining, Manson trichrome staining and histological scorings were done. The degree of acute hepatotoxicity was markedly lower in UIHA and 5 kGy than in 50 kGy GIHA pretreated group and there was negligible difference between 5 and 50 kGy GIHA pretreated group. The expression of interferon-gamma (IFN-gamma) was significantly (P<0.05) suppressed in 5 and 50 kGy GIHA pretreated group. Histological scorings showed a significant protection of liver in UIHA and 5 kGy GIHA pretreated mice. Expression of alpha class GSTs was significantly increased in 5 and 50 kGy GIHA pretreated group. To conclude suppression of IFN-gamma and increase in alpha-class GSTs expression may exert a protective role in acute hepatotoxicity of APAP and 5 kGy GIHA showed comparable protective effect to that of UIHA.
...
PMID:Effect of gamma irradiated hyaluronic acid on acetaminophen induced acute hepatotoxicity. 1823 25

The effects of caffeinated and non-caffeinated paracetamol administration, with or without vitamins A and E supplementation on the protein and enzyme levels in Wistar albino rats were investigated using caffeinated paracetamol and paracetamol as caffeinated and non-caffeinated paracetamol respectively, and water soluble acetic acid derivatives of vitamins A and E. Serum AST, ALT and ALP levels (u/l) significantly increased [P < 0.05] following paracetamol administration. Caffeination as well as administration of vitamins A and E caused significant decreases[P < 0.05] in AST and ALP levels in all test groups when co-administered with paracetamol and in ALT level except in the caffeinated paracetamol + Vitamin E group in which ALT and ALP level except in the caffeinated paracetamol + vitamin E group in which ALT and ALP levels significantly increased [P < 0.05]. Total serum protein level (g/100ml) significantly increased following caffeination as well as during co-administration of caffeinated paracetamol and Vitamin E; and significantly decreased during co-administration of paracetamol and vitamin A. Paracetamol administration without caffeination or supplementation with vitamin A and E can therefore cause increases in serum liver enzymes that is suggestive of liver necrosis which can be ameliorated to varying degrees by caffeine, vitamin A and E.
...
PMID:Serum protein and enzyme levels in rats following administration of antioxidant vitamins during caffeinated and non-caffeinated paracetamol induced hepatotoxicity. 1837 21

Acetaminophen (APAP) is one of the most commonly used drugs for the safe and effective treatment of fever and pain. However, it is a well-established hepatotoxin. The objective of this study was to identify alternation in various genes in liver of mice after administration of low and high doses of APAP. Male C57BL/6J mice received APAP (30 or 300 mg/kg, i.p.). They were sacrificed after 6 hr and 24 hr for assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total RNA isolation, cDNA microarray analysis and histopathological analysis of liver injury. Low dose of APAP did not cause hepatotoxicity in mice. However, it was toxic at a high dose. Using microarray technology, we selected changed genes more than 1.5 fold. Gene expression changes were recorded even at a low dose treatment with APAP. Six (6) hr after APAP treatment at low dose, 6 genes were up-regulated and 25 genes were down-regulated. However, 24 hr after treatment at low dose 8 genes were up-regulated and 34 genes were down-regulated. 6 hr after of high dose treatment 29 genes were down-regulated and none was up-regulated. A 24 hr treatment with high dose up-regulated 6 genes and down-regulated 18 genes. These expression patterns provide information on high versus low dose mechanisms of APAP toxicity. Gene expression signatures recorded after a nontoxic dose of APAP strongly support the validity of gene expression changes as meaningful markers of hepatotoxicity.
...
PMID:Effects of acetaminophen on hepatic gene expression in mice. 1847 68

Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague-Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level.
...
PMID:Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. 1851 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---