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)

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related to chemical administration. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane to rats were hepatocellular necrosis, karyomegaly, and biliary hyperplasia of the liver; renal tubule necrosis, regeneration, and karyomegaly of the kidney; and necrosis and inflammation of the nasal olfactory and respiratory epithelium. Groups of 20 male and 20 female mice received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg 5 days per week for up to 17 weeks; 30 male and 30 female mice received corn oil alone and served as controls. Sixteen male and seven female mice in the 250 mg/kg groups died by week 4. The final mean body weights and mean body weight gains of dosed mice were similar to those of the controls, except those of 250 mg/kg males, which were lower than those of controls. The principal toxic lesions associated with the administration of 1,2,3-trichloropropane were hepatocellular necrosis and karyomegaly of the liver; necrosis, regeneration, and hyperplasia of the bronchiolar epithelium in the lung; and acanthosis (hyperplasia) and hyperkeratosis of the forestomach epithelium. 2-Year Studies: Groups of 60 male and 60 female rats received 0, 3, 10, or 30 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 30 mg/kg as the high dose in these studies was based on the following chemical-related effects in the 17-week studies: deaths and liver and kidney lesions at 125 and 250 mg/kg and reduced final mean body weights and mean body weight gains at 63 mg/kg or greater. Groups of 60 male and 60 female mice received 0, 6, 20, or 60 mg 1,2,3-trichloropropane/kg body weight in corn oil by gavage 5 days per week for up to 104 weeks. Selection of 60 mg/kg as the high dose was based on chemical-related deaths and lesions of the liver, lung, and forestomach at 125 and 250 mg/kg in the 17-week studies. 15-Month Interim Evaluations: Up to 10 rats and 10 mice from each dose group were evaluated at 15 months. Absolute and relative liver and kidned kidney weights of dosed rats were significantly greater than those of the controls. Chemical-related nonneoplastic lesions and neoplasms of the forestomach, oral mucosa, pancreas (males), kidney, mammary gland (females), preputial gland, and clitoral gland were observed in dosed rats. Chemical-related nonneoplastic lesions and neoplasms of the forestomach and liver (females) were observed in dosed mice. Survival and Body Weight in the 2-Year Studies: Survival of male and female rats receiving 10 or 30 mg/kg 1,2,3-trichloropropane was significantly lower than that of controls. Two-year survival rates of male rats were: control, 34/50; 3 mg/kg, 32/50; 10 mg/kg, 14/49; 30 mg/kg, 0/52; and of females were: 31/50, 30/49, 8/52, 0/52. At 30 mg/kg, survival was markedly reduced due to chemical-related neoplasms, and survivors were killed in weeks 67 (females) or 77 (males). Final mean body weights of 30 mg/kg rats were 13% lower for males and 12% lower for females than those of controls; mean body weights of 3 and 10 mg/kg rats were similar to controls. Survival rates of mice receiving 6, 20, or 60 mg/kg 1,2,3-trichloropropane were also significantly lower than those of controls. Two-year survival rates of male mice were: 42/52, 18/51, 0/54, 0/56; and of female mice were: 41/50, 13/50, 0/51, 0/55. Because of reduced survival at 20 and 60 mg/kg due to chemical-related neoplasms, survivors were killed in weeks 73 (60 mg/kg females), 79 (60 mg/kg males), or 89 (20 mg/kg males and females). Final mean body weights were 16% lower for 60 mg/kg males, 18~ lower for 60 mg/kg females, and 13% lower for 20 mg/kg males than those of controls. Final mean body weights of 6 mg/kg males and females and 20 mg/kg females were similar to controls. Neoplasms and Nonneoplastic Lesions in the 2-Year Studies: Administration of 1,2,3-trichloropropane to rats induced benign and malignant neoplasms of the oral mucosa (pharynx and tongue), forestomach, and preputial and clitoral glands in males and females; benign neoplasms of the exocrine pancreas and kidney in males, and malignant neoplasms of the mammary gland in females. The incidences of squamous cell papillomas and carcinomas of the oral mucosa were significantly increased in 10 and 30 mg/kg rats, while the incidences of squamous cell papillomas or carcinomas (combined) of the forestomach were significantly increased in all dosed groups. The incidence of pancreatic acinar adenoma was significantly increased in dosed males, but not in dosed females. Similarly, the incidence of adenoma of the kidney was significantly increased in 10 and 30 mg/kg male rats only. The incidences of adenoma or carcinoma (combined) of the preputial gland in 30 mg/kg males and of the clitoral gland in 10 and 30 mg/kg females (homologous organs) were significantly increased. The incidence of adenocarcinoma of the mammary gland was significantly increased in the 10 and 30 mg/kg females. The incidences of Zymbal's gland carcinomas were increased in 30 mg/kg males and females. Adenocarcinomas of the intestine occurred in small numbers of dosed rats and may have been chemical related. In mice, the incidence of squamous cell carcinoma of the oral mucosa was significantly increased only in 60 mg/kg females. In contrast, the incidences of squamous cell papilloma and carcinoma of the forestomach were significantly increased in all groups of dosed mice. The incidences of hepatocellular adenoma or carcinoma (combined) were significantly increased in all dosed groups of males and 60 mg/kg females. The incidences of harderian gland adenoma were significantly increased in 20 mg/kg males and in 60 mg/kg males and females. The incidences of uterine adenoma, adenocarcinoma, and stromal polyp were significantly increased in 60 mg/kg females. Genetic Toxicology: 1,2,3-Trichloropropane was mutagenic in vitro in the presence of S9 metabolic activation. At two laboratories, positive responses were obtained for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535 in the presence of S9; no mutagenic activity was observed in TA1537, with or without S9. 1,2,3-Trichloropropane induced trifluorothymidine resistance in L5178Y mouse lymphoma cells with, but not without, S9. In cultured Chinese hamster ovary cells, sister chromatid exchanges and chromosomal aberrations were induced by 1,2,3-trichloropropane; however, significant increases in the endpoints of both cytogenetic effects occurred only in the presence of S9. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas of the pancreas and kidney, adenomas or carcinomas of the preputial gland, and carcinomas of the Zymbal's gland. Adenomatous polyps and adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female F344/N rats based on increased incidences of squamous cell papillomas and carcinomas of the oral mucosa and forestomach, adenomas or carcinomas of the clitoral gland, adenocarcinomas of the mammary gland, and carcinomas of the Zymbal's gland. Adenocarcinomas of the intestine may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in male B6C3F1 mice based on increased incidences of squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, and harderian gland adenomas. Squamous cell papillomas of the oral mucosa may have been related to chemical administration. There was clear evidence of carcinogenic activity of 1,2,3-trichloropropane in female B6C3F1, mice based on increased incidences of squamous cell carcinomas of the oral mucosa, squamous cell papillomas and carcinomas of the forestomach, hepatocellular adenomas or carcinomas of the liver, harderian gland adenomas, and uterine adenomas, adenocarcinomas, and stromal polyps. Nonneoplastic lesions associated with exposure to 1,2,3-trichloropropane included increased severity of nephropathy in male rats and increased incidences of basal cell and squamous hyperplasia of the forestomach, acinar hyperplasia of the pancreas, renal tubule hyperplasia, and preputial or clitoral gland hyperplasia in male and female rats. Increased incidences of squamous hyperplasia of the forestomach and eosinophilic foci in the liver in male and female mice were chemical related. Synonyms: Allyl trichloride, glycerol tnchlorohydrin, glyceryl tnchlorohydrin, trichlorohydrin
 ...
PMID:NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 52

The carotenoid lycopene has been touted as possessing various antioxidant properties, but there are no demonstrations that lycopene inhibits tissue injury due to acute oxidant stress. Thus, the present study examined the effects of intake of lycopene or tomato extract, a rich source of lycopene, on acute liver injury caused by the oxidant carbon tetrachloride (CCl4). Feeding with tomato extract (10% tomato powder), but not with lycopene (0.25% lycopene beadlets), partially inhibited CCl4-induced hepatic injury based on the serum activities of sorbitol dehydrogenase and aspartate aminotransferase. No effect was seen for either lycopene or tomato extract on serum beta-glucuronidase activity, a marker of lysosomal injury. We concluded that tomato extract, but not lycopene, partially protected against acute liver injury due to chemically-induced oxidant stress.
 ...
PMID:Effects of lycopene-beadlet or tomato-powder feeding on carbon tetrachloride-induced hepatotoxicty in rats. 1507 Jan 65

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.
 ...
PMID:Effect of taurine on biliary excretion and metabolism of acetaminophen in male hamsters. 1551 25

Microcystins are naturally occurring hepatotoxins produced by certain strains of Microcystis aeruginosa and microcystin-LR is the most toxic among the 60 microcystin variants isolated so far. These toxins have been implicated in both human and livestock mortality. In the present study we evaluated the age-dependent hepatotoxic effects of microcystin-LR (MC-LR) in mice after intraperitoneal and oral route of exposure. For acute toxicity studies by intraperitoneal route, 1 LD(50) dose of MC-LR (43.0 microg/kg) was administered to 6- to 36-week-old mice. Results showed that time to death in toxin treated animals decreased with age of mice. In comparison to control mice, treated animals of all age groups showed significant increases in liver body mass index and increases in serum enzymes (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, sorbitol dehydrogenase). For acute oral toxicity studies, 1 LD(50) of microcystin-LR containing extracts (3.5 g of MCE/kg) was administered to 6- and 36-week-old mice. The effects on biochemical variables were similar to intraperitoneal route of exposure. Significant age-dependent effects that were observed in microcystin treated animals by intraperitoneal and oral routes of exposure include: time to death, hepatic lipid peroxidation, glutathione depletion and DNA fragmentation. The age-dependent effects observed in some of the biochemical variables may be due to difference in the amount of microcystin-LR up take and also the age-dependent ability to detoxify the toxin in mice.
 ...
PMID:Age-dependent effects on biochemical variables and toxicity induced by cyclic peptide toxin microcystin-LR in mice. 1579 18

The aim of the study was to investigate the effect of the dietary fat on selected parameters of toluidines toxicity in rats during subchronic exposure. Three isomers of toluidine (ortho, meta, and para) were administered to rats in the diet for 1 and 3 months at levels 40, 80, 160 mg/kg/day in two kinds of diet containing either 4% or 14% fat. All doses of toluidine isomers produced a 1.5- to 9.8-fold increase in methemoglobin (MetHb) level during both treatment periods. A distinct dose-response relationship was observed, especially for o- and m-toluidine; the effect was generally greater in rats fed high-fat diet. Reduced glutathione level in liver was increased in all treated groups, 1.5- to 5.1-fold, irrespective of the kind of diet. An increase in hepatic lipid peroxidation (thiobarbituric acid reactive substances; TBARS), 1.5- to 4.5-fold, was noticed in the majority of the treated groups. Generally, there was no consistent effect of diet except for p-toluidine where the level of hepatic TBARS was lower in rats fed high-fat diet. Blood urea nitrogen (BUN) level in animals treated with all doses of o- and m-toluidine was 1.3- to 5.0-fold higher in comparison with respective controls. No clear relationship between BUN level and the kind of diet was found. No effect of toluidines on the activity of serum aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) were observed. In the majority of groups treated for 30 and 90 days the amount of toluidines in 24-h urine was lower in rats fed high-fat diet. Final body weight gain in rats treated with o- and p-toluidine (80 and 160 mg/kg body weight [b.w.]) was lower as compared to controls. In summary the high-fat diet stimulated methemoglobin formation in rats treated with o- and m-toluidine and cause the decrease in the amount of toluidines in 24-h urine. The high content of fat did not affect consistently the other parameters tested.
 ...
PMID:Effect of dietary fat on selected parameters of toxicity following 1- or 3-month exposure of rats to toluidine isomers. 1625 56

Effect of carbon tetrachloride (CCl(4)) pretreatment on the biotransformation and elimination of acetaminophen were examined in male mice. A 24 hr initial dose of CCl(4) (0.05 ml/kg, intraperitioneally) reduced the induction of hepatotoxicity resulting from acetaminophen treatment (350 mg/kg, intraperitoneally) as determined by changes in serum alanine and aspartate aminotransferase, and sorbitol dehydrogenase activities. Acetaminophen and the major metabolites in plasma were monitored for 12 hr following acetaminophen treatment. CCl(4) pretreatment decreased the plasma concentrations of acetaminophen-cysteine and acetaminophen-mercapturate, but acetaminophen-glucuronide and acetaminophen-sulfate were increased significantly. The elimination of the parent drug from plasma was not affected by CCl(4). In urine collected for 24 hr, the concentrations of acetaminophen-sulfate and acetaminophen-glucuronide were increased by 84% and 33%, respectively, whilst acetaminophen-cysteine and acetaminophen-mercapturate were reduced to approximately one third of control. Expression of cytochrome P450 (CYP) isozymes was determined using antibodies of 2E1 and 1A2 as probes. CYP2E1 and 1A2 expressions were decreased significantly by CCl(4). Likewise, CCl(4) treatment reduced the microsomal p-nitrophenol hydroxylase and p-nitroanisole O-demethylase activities to less than one third of control. The results indicate that, although CCl(4) reduces the generation of thioether conjugates of acetaminophen by decreasing the CYP activities, inhibition of the oxidative metabolism of acetaminophen is counterbalanced by the enhancement of conjugate formation via the glucuronide and sulfate pathways, resulting in elimination of the drug at a rate equivalent to that in normal mice. It is suggested that liver injury in patients may not warrant a mandatory reduction of drug doses extensively inactivated via phase II reactions.
 ...
PMID:Contrasting changes in phase I and phase II metabolism of acetaminophen in male mice pretreated with carbon tetrachloride. 1644

The effects of dimethylsulfoxide (DMSO) on the metabolism and toxicity of chlorinated methanes were examined. Male mice were treated with DMSO (1, 2.5 or 5 ml kg(-1), i.p.) prior to challenge with dichloromethane (CH(2)Cl(2)) or carbon tetrachloride (CCl(4)). Blood carboxyhemoglobin elevation resulting from metabolic conversion of CH(2)Cl(2) to carbon monoxide was inhibited dose-dependently by DMSO pretreatment. The elevation of serum aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase activities induced by CCl(4) (0.1 mmol kg(-1)) was not changed in mice pretreated with DMSO at 1 ml kg(-1), but depressed significantly at a greater dose of DMSO. However, DMSO failed to alter the hepatotoxicity of CCl(4) injected at a dose of 0.2 mmol kg(-1). DMSO induced the microsomal p-nitrophenol hydroxylase and p-nitroanisole O-demethylase activities as early as 2 h following the treatment. Microsomal disposition of CH(2)Cl(2) and CCl(4) was measured using a vial equilibration technique. The disappearance of CH(2)Cl(2) was inhibited competitively by addition of DMSO. But DMSO did not affect the metabolic degradation of CCl(4). The results indicate that DMSO has multiple effects on metabolism and toxicity of xenobiotics. DMSO induces the hepatic metabolizing activity mediated by CYP2E1, but the presence of this solvent in the enzyme site may inhibit directly the enzymatic interaction with a substrate. The toxicological significance of DMSO-induced effects on such an interaction may be variable depending on the properties of each substrate. The invulnerability of CCl(4) metabolism to the effects of DMSO appears to be related to its high affinity for the lipophilic CYP enzyme site.
 ...
PMID:Comparative effects of dimethylsulfoxide on metabolism and toxicity of carbon tetrachloride and dichloromethane. 1717 72

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

Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 microg/kg b.m./24 h) or alpha-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed, livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG), and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development.
 ...
PMID:The influence of methionine, selenomethionine, and vitamin E on liver metabolic pathways and steatosis in high-cholesterol fed rabbits. 1791 70

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early clinical trials.
 ...
PMID:The current state of serum biomarkers of hepatotoxicity. 1829 70


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