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)

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 micromol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P<0.05) and liver (**P<0.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P<0.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.
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PMID:Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. 1060 94

Tamoxifen (TAM) is used in the treatment of breast cancer and decreases the incidence of breast cancer when given to healthy women for different therapeutic purposes. This expansion of its use calls for further studies of its own potential side effects and those in combination with other prescription drugs. Diazepam (DP) is one such drug normally administered to patients who are under cancer treatment and those who suffer from insomnia. The present study examines the effect of individual and simultaneous administration of TAM and DP at therapeutic dose level of 0.8 mg/Kg/day of TAM and 0.3 mg/Kg/day of DP to normal female Wistar rats for a period of 12 weeks. The drugs were administered orally by mixing it in pellet made by wheat dough. There was no significant change in the terminal body weight and liver weights of animals. The ovary weights in TAM + DP treated animals were significantly decreased. The serum succinate dehydrogenase (SDH) levels were significantly lower in TAM, DP and TAM + DP treated rats and comparatively were lowest in TAM and TAM + DP treated animal groups. Serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), acid and alkaline phosphatase (ACP & ALP) levels were significantly higher in the three treated groups, but comparatively lower in TAM + DP treated animals when compared to TAM or DP alone treated rats. There was marked increase in liver triglyceride and cholesterol levels in the three treated groups but remarkable decrease in liver glycogen. Total serum cholesterol levels were significantly high in DP and TAM + DP treated rats and total serum triglyceride levels were significantly high only in TAM treated rats. As a whole it can be concluded that DP does not enhance TAM toxicity on simultaneous administration, but on its own when administered individually brings about perturbation in lipid storage and metabolism.
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PMID:A toxicity study of simultaneous administration of Tamoxifen and Diazepam to female Wistar rats. 1066 14

Freeze dried Eupatorium adenophorum leaf powder mixed in rat feed at a level of 25% elicited hepatotoxicity. The affected animals were jaundiced and had marked increase in plasma bilirubin levels and activities of alkaline phosphatase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase. The liver of intoxicated animals had focal areas of necrosis and bile duct proliferation. Elevation in plasma bilirubin concomitant with alterations in enzyme profile and histopathological lesions are consistent with liver injury and cholestasis. This is the first report of the toxicity of E. adenophorum to rats.
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PMID:Hepatotoxicity of Eupatorium adenophorum to rats. 1066 12

Ampelopsis brevipedunculata (Maxim.) Trautv. (Vitaceae) has been used in Japanese herbal folk medicine to treat liver disease. The objective of this study is to evaluate the antihepatotoxic effect of A. brevipedunculata in the mice. An aqueous fraction was extracted by immersing the berries of the plant material in 40% ethanol for six months, followed by removing ethanol. Daily free access to the aqueous extract as drinking water greatly reduced the severity of hepatic injury, characterized by centrilobular necrosis, cytoplasmic vacuolation, cellular swelling, inflammation, and fibrosis in the mice receiving a nonlethal dose of carbon tetrachloride twice weekly during nine weeks. In addition, such a feeding regimen decreased the elevated levels of plasma glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in the carbon tetrachloride-administered mice. These results suggest that the feeding regimen with A. brevipedunculata extract inhibited a progression of hepatic injury induced by carbon tetrachloride.
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PMID:Ampelopsis brevipedunculata (Vitaceae) extract inhibits a progression of carbon tetrachloride-induced hepatic injury in the mice. 1119 78

The antipyretic effect of nimesulide has not been adequately compared with paracetamol and ibuprofen-paracetamol combination in children. Hence, a randomized, double blind, and parallel groups' design and multicenter study was conducted on children with respiratory tract infections. Eighty-nine patients with temperatures above 38.5 degrees C were randomly administered nimesulide (1.5 mg/kg/dose), paracetamol (10.0 mg/kg/dose), or ibuprofen-patients combination (10.0 mg/kg/dose), thrice daily for five days. The axillary temperature was recorded at the baseline and at different time intervals post administration of drugs. The hematological and biochemical investigations were performed at the basal level and at the end of the treatment period. The adverse drug reactions were monitored during the trial. All the drugs produced a significant fall in temperature as compared to their respective basal values (p < 0.001). However, on looking at the change in temperatures at different time intervals from the respective basal levels, no significant difference was found among all the drugs. Surprisingly, nimesulide had a tendency to raise serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase levels as compared to its baseline values. There was no marked adverse effect of the drugs on other hematological and biochemical parameters investigated. No other serious adverse reaction occurred in the study. Ibuprofen-paracetamol combination, nimesulide, and paracetamol had almost similar antipyretic effects in children.
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PMID:Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol. 1126 83

The alcoholic extract of Acanthus ilicifolius leaves inhibited the formation of oxygen derived free radicals (ODFR) in vitro with IC(50) of 550 microg/ml, 2750 microg/ml, 670 microg/ml and 600 microg/ml (Fe(2+)/ascorbate system), 980 microg/ml (Fe(3+)/ADP/ascorbate system) for superoxide radical production, hydroxyl radical generation, nitric oxide radical formation and lipid peroxide formation, respectively. The oral administration of the extract (250 and 500 mg/kg) significantly reduced CCl(4) induced hepatotoxicity in rats, as judged from the serum and tissue activity of marker enzymes [glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP)]. These results were comparable with those obtained with curcumin (100 mg/kg, p.o.).
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PMID:Antioxidant and hepatoprotective effect of Acanthus ilicifolius. 1129 3

The hepatoprotective activity of the aqueous-methanolic extract of Ambrosia maritima was investigated against acetaminophen (paracetamol, 4-hydroxy acetanilide) induced hepatic damage. Acetaminophen at the dose of 640 mg/kg produced liver damage in rats as manifested by the significant (P < 0.001) rise in serum levels of glutamate oxaloacetate transaminase (AST), glutamate pyruvate transaminase (ALT) and alkaline phosphatase (ALP) to 1178.5 +/-118.05; 607.5 +/- 32.6 and 274.16 +/- 8.89 IU/l (n = 10), respectively, compared with respective control values of 97.83+/-3.23; 46.0 +/- 3.92 and 168.67 +/- 7.86 IU/l. Pretreatment of rats with the plant extract (100 and 200 mg/kg) lowered significantly (P < 0.001) the respective serum AST to 203.3+/-5.74 and 157.1 +/- 8.78 IU/l, ALT to 138.67 +/- 7.7 and 87.5 +/- 3.6 IU/l and ALP levels to 238.0 +/- 5.89 and 206.5 +/- 7.5 IU/l, respectively. Treatment of rats with acetaminophen led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA) (42%). This was associated with a significant reduction of the hepatic antioxidant system e.g. reduced glutathione (GSH) (65%), glutathione reductase (GSH-R) (35%), total glutathione peroxidase (GSH-Px) (32%) and glutathione-S-transferase (GST) (16%). These biochemical alterations resulting from acetaminophen administration were inhibited by pretreatment with A. maritima L. extract. These data suggest that the plant A. maritima L. may act as a hepatoprotective and antioxidant agent.
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PMID:Evaluation of the protective potential of Ambrosia maritima extract on acetaminophen-induced liver damage. 1129 46

The efficacy and toxicity of combined paclitaxel and gemcitabine was evaluated in 54 chemotherapy-naive patients with metastatic non-small cell lung cancer (NSCLC). Gemcitabine i.v. 1000 mg/m(2)was administered on days 1 and 8 and paclitaxel 200 mg/m(2)as a continuous 3-hour infusion on day 1. Treatment was repeated every 21 days. Patients had a median age of 53 years. ECOG performance status was 0 or 1 in 48 patients. 41 patients (75.9%) had initial stage IV disease; histology was mainly adenocarcinoma (46.3%). 2 patients (4.3%) achieved a complete response and 15 (31.9%) achieved a partial response giving an overall response rate of 36.2% (95% CI: 22.4-49.9%); 19 patients (40.4%) had stable disease and 10 (21.3%) had progressive disease. The median survival time was 51 weeks (95% CI: 46.5-59.3), with a 1-year survival probability of 0.48 (95% CI: 0.34-0.63). Grade 3/4 neutropenia and febrile neutropenia occurred in 15.2% and 2.2% of courses, respectively. Grade 3/4 thrombocytopenia was rare (1.8% of courses). Peripheral neurotoxicity developed in 25 patients (47.2%), mostly grade 1/2. Arthalgia/myalgia was observed in 30 patients (56.6%), generally grade 1 or 2. Grade 3 abnormal levels of serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) occurred in 5 patients (9.4%) and 1 patient (1.9%), respectively. Combined paclitaxel and gemcitabine is an active and well-tolerated regimen for the treatment of advanced NSCLC, and warrants further investigation in comparative, randomized trials.
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PMID:Combined paclitaxel and gemcitabine as first-line treatment in metastatic non-small cell lung cancer: a multicentre phase II study. 1133 67

N,N-Dimethylformamide (DMF) has excellent solvent properties and is used intensively in the production of synthetic leather and resins. It has caused hepatoxicity in human and animal studies. Hepatitis B virus (HBV) and hepatitis C virus infections are reported to be the major causes of chronic liver diseases (including liver cirrhosis and liver cancer) in Taiwan. This study examined the dose-response relationship of the observed abnormal liver function among the DMF-exposed workers and the interactions among DMF, other chemical exposures, HBV infection, and potential confounders on liver abnormalities. The average DMF exposure concentration was 11.6 ppm (median, 5.9 ppm; range, 0.1 to 86.6 ppm); 65 of 176 workers (36.9%) had high (> 10 ppm) DMF exposure, 37 (21%) had middle (> 5 ppm, < or = 10 ppm) exposure, and 74 (42%) had low (< or = 5 ppm) exposure. There were 24 of 65 abnormal liver function test results (LFTs) (36.9%) (elevations of either glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, or gamma-glutamyl transpeptidase) among the workers with high DMF exposure, 10 of 37 abnormal LFTs (27%) among workers with middle DMF exposure, and 11 of 74 abnormal LFTs (22%) among workers with low DMF exposure. Compared with the workers having low DMF exposure, the HBV, drinking, body mass index (BMI), sex, duration of employment, epichlorohydrin, and toluene exposure adjusted odds ratios (ORs) (and 95% confidence intervals [CIs]) for abnormal LFTs were 1.62 (0.61, 4.28) for workers with middle DMF exposure and 2.93 (1.27, 6.8) for those with high DMF exposure, and there was a significant dose response between DMF exposure and the prevalence of abnormal LFTs (P = 0.006). There were significant associations between abnormal LFTs and HBV carriers (adjusted OR: 3.11; 95% CI: 1.29, 7.5; P = 0.01) and between abnormal LFTs and increased BMI (adjusted OR: 2.2; 95% CI: 1.02, 4.72; P = 0.041). Ultrasonography showed significant associations between chronic liver diseases and HBV carrier status, increased BMI, and high cumulative (> 100 ppm-years) DMF exposure (respectively, adjusted OR: 9.58, 95% CI: 1.79, 51.4, P = 0.007; adjusted OR: 13.2, 95% CI: 1.32, 132, P = 0.025; and adjusted OR: 6.2, 95% CI: 1.14, 34.1, P = 0.032). Drinking and BMI were significantly associated with fatty liver (respectively, adjusted OR: 4.9, 95% CI: 1.39, 17.3, P = 0.012; and adjusted OR: 7.93, 95% CI: 1.6, 39.3, P = 0.01). In conclusion, this study demonstrated that (1) a significant dose-response relationship existed between liver function abnormalities and DMF exposure among workers in Taiwan, (2) HBV carrier status or increased BMI had synergistic effects with DMF in causing liver abnormalities (abnormal LFTs and clinical chronic liver diseases).
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PMID:Abnormal liver function associated with occupational exposure to dimethylformamide and hepatitis B virus. 1138 83

Acute hepatic failure was induced experimentally in rats by intraperitoneal injection of 2.5 mL kg(-1) carbon tetrachloride (CCl4), and the effects on the expression and function of P-glycoprotein in the liver, kidney and brain were evaluated. The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate). In rats with acute hepatic failure, the hepatic P-glycoprotein concentration increased 1.5-fold and the ATP concentration decreased to approximately 40% that in control rats. In contrast, P-glycoprotein concentrations in the kidney and brain and ATP concentrations in the kidney remained unchanged. The in-vivo P-glycoprotein function in these tissues was suppressed as evaluated by biliary and renal secretory clearances and brain distribution of rhodamine 123, a P-glycoprotein substrate. These findings suggest that factors other than P-glycoprotein concentration are involved in the systemic suppression of P-glycoprotein function in diseased rats. In Caco-2 cells, plasma collected from CCl4-treated rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of rhodamine 123 than that from control rats, suggesting the accumulation of an endogenous P-glycoprotein substrate/inhibitor in the plasma of diseased rats. In fact, the plasma concentration of corticosterone, an endogenous P-glycoprotein substrate, increased 2-fold in CCl4-treated rats compared with control rats. It was demonstrated that P-glycoprotein function is systemically suppressed in rats with CCl4-induced acute hepatic failure, not only in the target organ (liver), but also in other organs (kidney and brain), although the P-glycoprotein concentration remained unchanged in the kidney and brain, and increased in the liver. In the systemic suppression of the P-glycoprotein function in the diseased state, the alteration of plasma concentrations or components of endogenous P-glycoprotein-related compounds, such as corticosterone, would likely be involved.
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PMID:Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure. 1142 64


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