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)

Bacterial endotoxin (lipopolysaccharide; LPS) given to animals in large doses results in pronounced, midzonal liver injury. Exposure to smaller, non-injurious doses of LPS augments the toxicity of certain hepatotoxicants. This study was conducted to delineate the development of injury in a rat model of augmentation of aflatoxin B(1) (AFB(1)) hepatotoxicity by LPS. At large doses (i.e., > 1 mg/kg, ip), AFB(1) administration resulted in pronounced injury to the periportal regions of the liver. Male, Sprague-Dawley rats (250-350 g) were treated with 1 mg AFB(1)/kg, ip or its vehicle (0.5% DMSO/saline) and 4 h later with either E. coli LPS (7.4 x 106 EU/kg, iv) or its saline vehicle. Liver injury was assessed 6, 12, 24, 48, 72, or 96 h after AFB(1) administration. Hepatic parenchymal cell injury was evaluated as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and from histologic examination of liver sections. Biliary tract alterations were evaluated as increased concentration of serum bile acids and activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5'-ND) in serum. At all times and for all markers, injury in rats treated with either AFB(1) or LPS alone was absent or modest. In the AFB(1)/LPS cotreated group, hepatic parenchymal cell injury was pronounced by 24 h and had returned to control values by 72 h. The injury began in the periportal region and spread midzonally with time. Furthermore, changes in serum markers indicative of biliary tract alterations were evident by 12 h and had returned to control values by 72 h. Thus, the nature of the hepatic lesions suggested that LPS potentiated the effects of AFB(1) on both parenchymal and bile duct epithelial cells.
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PMID:Bacterial lipopolysaccharide exposure augments aflatoxin B(1)-induced liver injury. 1082 77

The effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria on hepatotoxicity and lipid peroxidation induced by 2-acetylaminofluorene (2-AAF) in rats was investigated. The ability of butylated hydroxyanisole (BHA) to attenuate the toxic effect of 2-AAF was also examined. Kolaviron administered orally to rats at a dose of 100mg/kg body weight twice a day for 1 week before challenge with 2-AAF (200mg/kg feed) and continuously for 3 weeks at a single dose of 200mg/kg body weight reversed the 2-AAF-mediated decrease in final body weight and relative organ weights, especially the liver. BHA was administered at a dose of 7.5g/kg feed to the animals for 4 weeks. The extract decreased significantly the 2-AAF-mediated increase in the activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase and ornithine carbamyl transferase by 58%, 62%, 60% and 67%, respectively. BHA elicited respectively 55%, 63%, 57% and 65% reduction in the 2-AAF induced-increase in the activities of these enzymes. Histological examination of the liver slices correlated with the changes in serum enzyme alterations. Similarly, kolaviron decreased the 2-AAF reduction of 5'-nucleotidase and glucose-6-phosphatase activities by 63% and 60%, respectively while BHA elicited 59% and 61% decrease in the activities of these enzymes. Simultaneous administration of kolaviron with 2-AAF inhibited microsomal lipid peroxidation as assessed by the thiobarbituric acid reacting substances (TBARS) formation by 66%. BHA produced a 64% reduction in TBARS formation. In the present study, kolaviron appears to act as an in vivo natural antioxidant and an effective hepatoprotective agent and is as effective as BHA.
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PMID:Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron--a Garcinia kola seed extract. 1082 5

Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants including aflatoxin B(1) (AFB(1)). Mediators of inflammation, in particular neutrophils (PMNs), are responsible for tissue injury in a variety of animal models. This study was conducted to examine the role of PMNs in the pathogenesis of hepatic injury after AFB(1)/LPS cotreatment. Male, Sprague-Dawley rats (250-350 g) were treated with either 1 mg AFB(1)/kg, ip or its vehicle (0.5% DMSO/saline), and 4 h later with either E. coli LPS (7. 4 x 10(6) EU/kg, iv) or its saline vehicle. Over a course of 6 to 96 h after AFB(1) administration, rats were killed and livers were stained immunohistochemically for PMNs. LPS resulted in an increase in PMN accumulation in the liver that preceded the onset of liver injury. To assess if PMNs contributed to the pathogenesis, an anti-PMN antibody was administered to reduce PMN numbers in blood and liver, and injury was evaluated. Hepatic parenchymal cell injury was evaluated as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and from histologic examination of liver sections. Biliary tract alterations were evaluated as increased concentration of serum bile acids and activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5'-ND) in serum. Neutrophil depletion protected against hepatic parenchymal cell injury caused by AFB(1)/LPS cotreatment but not against markers of biliary tract injury. This suggests that LPS augments AFB(1) hepatotoxicity through two mechanisms: one of which is PMN-dependent, and another that is not.
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PMID:Lipopolysaccharide augments aflatoxin B(1)-induced liver injury through neutrophil-dependent and -independent mechanisms. 1105 57

Eupatorium adenophorum (Crofton weed), a native of Central America. has appeared as a major weed in several areas in different parts of the world. Horses that eat this plant are poisoned on prolonged exposure. Toxicity due to consumption of this plant by other grazing animals is not clear. Administration of freeze-dried leaf powder to mice results in hepatotoxicity. Earlier attempts to produce toxicity in rats using the leaves of this plant were not successful. In the present study, administration of oven-dried E. adenophorum leaves collected at the flowering stage elicited hepatotoxicity in rats. The affected animals had a marked increase in the concentration of plasma bilirubin and in the activities of 5'-nucleotidase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. There were no significant differences in plasma creatinine, urea or total protein values in the affected animals compared to controls. The livers of the affected animals had focal areas of necrosis throughout the parenchyma and hepatocytes showed megalocytosis. The bile ducts were dilated and the epithelium showed degenerative to necrotic changes. The alterations in bilirubin, enzymes and histopathological changes imply cholestasis and liver injury.
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PMID:Biochemical alterations in the blood plasma of rats associated with hepatotoxicity induced by Eupatorium adenophorum. 1158 83

Eupatorium adenophorum leaves cause hepatotoxicity and cholestasis in rats. The hepatotoxicant has been characterized as 9-oxo-10,11-dehydroageraphorone (ODA), a cadinene sesquiterpene. Oral administration of ODA, mixed in feed to rats, caused jaundice in 24 h. The liver of the intoxicated animals had focal areas of hepatocellular necrosis, proliferation, and dilation of bile ducts with degenerative changes in the lining epithelium. There was marked increase in the conjugated form of plasma bilirubin and in the activities of the enzymes glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, glutamate dehydrogenase, and 5'-nucleotidase. The histopathological lesions in liver and biochemical profile of marker enzymes show that ODA induced hepatotoxicity and cholestasis in rats. This is the first report on the toxicity of a cadinene sesquiterpene in rats.
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PMID:Hepatotoxicity and cholestasis in rats induced by the sesquiterpene, 9-oxo-10,11-dehydroageraphorone, isolated from Eupatorium adenophorum. 1183 25

Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and mice of each sex; this lesion was more severe in rats than in mice. Inflammation of the liver, periportal to midzonal in distribution, occurred in rats in the 8000 and 16,000 ppm groups. Depletion of hematopoietic cells was evident in rats of each sex in the bone marrow (8000 and 16,000 ppm) and spleen (16,000 ppm). Kidneys of male and female rats in the 4000, 8000, and 16,000 ppm groups had an increased number and size of protein droplets in the epithelia of the renal cortical tubules. In the 13-week feed studies, groups of 10 rats per sex received diets containing 500 to 8000 ppm cupric sulfate, and groups of 10 mice per sex received diets containing 1000 to 16,000 ppm cupric sulfate for 92 days; estimates of cupric sulfate consumption ranged from 32 to 551 mg/kg per day for rats and 173 to 4157 mg/kg per day for mice. There were no chemical-related deaths in rats or mice, and no clinical signs of cupric sulfate toxicity were recorded. Final mean body weights were lower than those of the controls for animals of both species receiving doses of 4000 ppm cupric sulfate and greater. In mice in the 13-week studies, there was a dose-related decrease in liver weights. Hematologic, clinical chemistry, and urinalysis evaluations of rats in the 13-week study revealed variable chemical-related changes that were, for the most part, restricted to the 4000 and 8000 ppm groups. Increases in serum alanine aminotransferase and sorbitol dehydrogenase activities in both sexes were indicative of hepatocellular damage, as were increases in 5'-nucleotidase and bile salts in males. Decreases in mean cell volume, hematocrit, and hemoglobin indicated the development of a microcytic anemia, while increases in reticulocyte numbers at the same time points suggested a compensatory response to the anemia by the bone marrow. Increases in urinary glucose and N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) and aspartate aminotransferase (alpha-cytosolic enzyme) were suggestive of renal tubule epithelial damage. Dose-related increases in copper occurred in all male rat tissues examined (lissues examined (liver, kidney, plasma, and testis). These increases were accompanied by increases in zinc in the liver and kidney. Plasma calcium was significantly reduced in the 4000 and 8000 ppm groups, and there was a trend toward reductions in calcium in the kidney and testis as well. In the 8000 ppm group, plasma magnesium was significantly increased relative to the controls. Rats in the three highest dose groups had hyperplasia and hyperkeratosis of the forestomach, inflammation of the liver, and increases in the number and size of protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. These effects were similar to those seen in the 2-week feed study, and the incidence and severity of these lesions were dose related. Many of the droplets in male rat kidneys were large and had irregular crystalline shapes. These droplets stained strongly positive for protein but were negative by iron, PAS, and acid-fast (lipofuscin) staining methods. α-2-Microglobulin was present in the droplets of male rats, but there was no dose- related, qualitative difference in the content of this protein. In the 4000 and 8000 ppm groups, copper was distributed in a periportal to midzonal pattern in the liver and was restricted to the cytoplasm of the proximal convoluted tubule epithelium in the kidney. Copper was present in some, but not all, of the protein droplets. Transmission electron microscopy of the livers of rats of each sex revealed increases in the number of secondary lysosomes in hepatocytes in the periportal area. In mice of each sex receiving 4000 ppm cupric sulfate and higher in the 13-week study, there was a dose-related increase in hyperplasia with hyperkeratosis of the squamous mucosa on the limiting ridge of the forestomach. Minimal positive staining for copper was present in the liver and was limited to high-dose (16,000 ppm) male and female mice. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. In summary, administration of cupric sulfate to rats in feed or drinking water resulted in significant gastric changes and hepatic and renal damage. The primary lesion in rats was an increase in the size and number of proteinaceous droplets in the epithelial cytoplasm and lumen of the proximal convoluted tubule. For rats in the 13-week study, the no-observed-adverse-effect level (NOAEL) for evidence of histologic injury to the kidney was 1000 ppm for males and 500 ppm for females, while the NOAEL for liver inflammation was 1000 ppm for males and 2000 ppm for females. Hyperplasia with hyperkeratosis of the epithelium on the limiting ridge separating the forestomach from the glandular stomach was also seen in rats of each sex, and the NOAEL for this change was 1000-ppm cupric sulfate in the feed. Additionally, clinical pathology alterations noted in the 13-week study, along with histologic changes in bone marrow noted in the 2-week feed study, were indicative of a microcytic anemia with a compensatory bone marrow response. Mice appeared to be much more resistant to the toxic effects of cupric sulfate than rats. The primary target tissue in mice was the epithelium of the limiting ridge of the forestomach. The NOAEL for the hyperplasia and hyperkeratosis seen at this site in mice was 2000-ppm cupric sulfate in the feed. Synonyms: Chalcanthite; Copper sulfate; cupric sulfate pentahydrate; bluestone; blue vitriol; Roman vitriol; Salzburg vitriol. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)
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PMID:NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice. 1220 95

The effect of sodium selenite (Se) was investigated against two-stage rat liver carcinogenesis initiated by a single intraperitoneal injection of N-nitrosodiethylamine (DEN, 200 mg kg(-1) i.p.) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. Se (4 p.p.m.) was administered per os daily throughout the entire experiment, before the initiation, or during the promotion stage. The plasma, liver (hepatoma and surrounding tissue) and kidney tissue were investigated biochemically for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and 5'-nucleotidase. These enzyme activities were increased (p < 0.001) in plasma of hepatoma-bearing rats compared with normal control rats. The elevation of these enzyme activities in plasma was indicative of the persistent deteriorating effect of DEN in cancer-bearing animals. Aminotransferase levels were decreased in hepatoma and surrounding liver tissue, whereas lactate dehydrogenase, alkaline phosphatase and 5'-nucleotidase were increased in the cancer condition. These enzyme activities were reversed to near normal control values in animals treated with Se. It is apparent that the beneficial effect of Se is primarily exerted on the initiation phase and secondarily during the promotion stage of DEN-initiated rat liver carcinogenesis. The analysis of marker enzyme activities taken together with our previous findings clearly indicates the antitumour efficacy of sodium selenite on DEN-induced hepatoma animals.
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PMID:Sodium selenite modulates tumour marker indices in N-nitrosodiethylamine-initiated and phenobarbital-promoted rat liver carcinogenesis. 1273 4

To elucidate the potential factors modulating exposure to aflatoxin B1 (AFB1) in three Chinese populations, an epidemiologic study was conducted in Fusui County and Nanning City of Guangxi Province and Chengdu City of Sichuan Province. The incidence rates of hepatocelluar carcinoma (HCC) for males in these three regions were 92-97 per 100,000, 32-47 per 100,000, and 21 per 100,000, respectively. Eighty-nine residents from Fusui, 196 residents from Nanning, and 118 residents from Chengdu were screened for AFB1-albumin adduct (AAA) levels and hepatitis virus (HBV, HCV, HDV, HEV, and HGV) infections, as well as liver biochemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], y-glutamyl transpeptidase [GGT], 5'-nucleotidase, globulin [GLO], direct bilirubin, indirect bilirubin, and bile acid levels). At least one marker of hepatitis virus (HV) infection was present in 47.2% (42/89) of subjects from Fusui, while in Nanning and Chengdu the values were 15.8% (31/196) and 22.0% (26/118), respectively. In contrast to females, a higher level of AAA was observed in males; the difference was statistically significant in both the Nanning (P = 0.023) and the Chengdu (P = 0.026) subjects. In the Chengdu group, there was a significantly higher level of AAA in cases with HV infection (P = 0.041). There was a close association between AAA level and BMI in the adults without HV infection (r = 0.148, P = 0.044). Also, AAA was closely associated with DBIL and GGT in non-HV-infected minors (P < 0.05), closely associated with ALB, GLO, and GGT in HV-infected minors (P < 0.05), and closely associated with IBIL, GLO, TBA, and AST in non-HV-infected adults (P < 0.01). The co-effect of HV infection and AFB1 exposure may be responsible for the high risk of HCC in the Fusui region, whereas age, gender, BMI, and HV infection may modify individual aflatoxin levels. The relationship between AAA level and liver biochemistry indicates injury induced by aflatoxin to both hepatic parenchyma and biliary tract. But the associations vary with age and HV infection status.
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PMID:Associated factors in modulating aflatoxin B1-albumin adduct level in three Chinese populations. 1581 Jun 36

One of the focuses in current cancer chemoprevention studies is the search for nontoxic chemopreventive agents that inhibit the initiation of malignant transformation. Cancer biomarkers are quantifiable molecules involved in the physiologic or pathologic events occurring between exposure to carcinogens and the development, progression of cancer. Biomarkers may be the consequence of a continuous process, such as increased cell mass, or a discrete event, such as genetic mutation. Analysis of tumor markers can be used as an indicator of tumor response to therapy. Gallic acid is a naturally available polyphenol, possess strong antioxidant activity with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated the antiproliferative effect of gallic acid during diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in male wistar albino rats. DEN treatment resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen, argyophillic nucleolar organizing regions, and proliferating cell nuclear antigen. Gallic acid treatment significantly attenuated these alterations and decreased the levels of AgNORs and PCNA. These finding suggests that gallic acid is a potent antiproliferative agent against DEN-induced HCC.
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PMID:Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma. 1862 14

The ketogenic diet (KD) is a high-fat and low-carbohydrate diet, used for treating refractory epilepsy in children. We have previously shown alterations in nucleotidase activities from the central nervous system and blood serum of rats submitted to different models of epilepsy. In this study we investigated the effect of KD on nucleotidase activities in the blood serum, as well if KD has any influence in the activity of liver enzymes such as alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities in Wistar rats submitted to the lithium-pilocarpine model of epilepsy. At 21 days of age, rats received an injection of lithium chloride and, 18-19 h later, they received an injection of pilocarpine hydrochloride for status epilepticus induction. The results reported herein show that seizures induced by lithium-pilocarpine elicit a significant increase in ATP hydrolysis and alkaline phosphatase activity, as well as a decrease in ADP hydrolysis and aspartate aminotransferase activity. The KD is a rigorous regimen that can be associated with hepatic damage, as shown herein by the elevated activities of liver enzymes and 5'-nucleotidase in blood serum. Further studies are necessary to investigate the mechanism of inhibition of lithium on nucleotidases in blood serum.
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PMID:Effect of ketogenic diet on nucleotide hydrolysis and hepatic enzymes in blood serum of rats in a lithium-pilocarpine-induced status epilepticus. 2044 57


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