Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetaminophen is eliminated primarily by glucuronidation, thereby avoiding cytochrome P450-catalyzed bioactivation to a toxic reactive intermediate. Previous studies have shown that UDP-glucuronosyltransferase-deficient Gunn rats are more susceptible to acetaminophen toxicity than normal Wistar controls, from which the Gunn strain was derived. However, the Gunn and Wistar strains are not congenic, and differences in toxicologic susceptibility could be due in part to genetic differences other than UDP-glucuronosyltransferase activity. Accordingly, acetaminophen (750 mg/kg, ip) was administered to congenic RHA rats with normal (homozygous, RHA/++), moderately deficient (heterozygous, RHA/j+), and severely deficient (homozygous jaundiced, RHA/jj) activities of bilirubin UDP-glucuronosyltransferase. Acetaminophen metabolites were measured by high-performance liquid chromatography and production of the acetaminophen glucuronide conjugate was quantified by the area under plasma concentration-time curve (AUC) from 0 to 2 hr, standardized by the AUC value for acetaminophen in the same animal (glucuronidation ratio = AUC acetaminophen glucuronide/AUC acetaminophen). The 0- to 2-hr time period for AUC calculations was necessitated by the accumulation at later time points of glucuronide and sulfate conjugates in the plasma of animals experiencing severe nephrotoxicity. Acetaminophen bioactivation was quantified by the 24-hr urinary recovery of glutathione-derived conjugates. Hepatotoxicity and nephrotoxicity were assessed respectively by the peak concentrations of plasma alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Glucuronidation of acetaminophen in RHA/jj rats (0.065 +/- 0.005) (mean +/- SE) was reduced 63% compared to the RHA/++ controls (0.17 +/- 0.01) (p < 0.05). RHA/jj rats demonstrated respective 230- and 7-fold increases in the peak plasma concentrations of ALT (17144 +/- 1014 vs 75 +/- 10) and BUN (128 +/- 23 vs 18.4 +/- 0.2) compared to congenic normal controls (RHA/++) (p < 0.05). Heterozygous animals (RHA/j+) demonstrated intermediary toxicity for both parameters (ALT = 2029 +/- 1581, BUN = 41 +/- 16, p < 0.05). Decreased glucuronide production correlated with elevations in ALT (r = -0.86, p < 0.001), while increased acetaminophen bioactivation correlated directly with both elevated ALT (r = 0.93, p < 0.001) and BUN (r = 0.83, p = 0.001). These results using congenic controls demonstrate that the enhanced susceptibility of UDP-glucuronosyltransferase-deficient rats to acetaminophen toxicity is due to decreased glucuronidation resulting in enhanced bioactivation, rather than to other unappreciated genetic differences.
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PMID:Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glucuronosyltransferase. 144 Jun 17

The alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maize Linn.) at 50, 100 and 150 mg kg-1 daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses. The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maize Linn.) are not significantly toxic at low and medium doses (50 and 100 mg kg-1).
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PMID:Haematological and hepatotoxic effects of silken styles of corn in albino rats. 144 82

Milk production of dairy cows in 14 herds was increased by 3.8-32.1% by the administration of recombinant methionyl bovine somatotropin (bST) in a sustained-release vehicle at 14 d intervals at 40-94 d post partum. A greater response in multiparous than in primiparous cows was found in cows turned out to graze spring pasture. Administration of recombinant bST resulted in elevated plasma bST during the first 9 d after injection. Clinical characteristics such as respiration, heart rate and body temperature were unaffected by bST treatment, as were blood erythrocyte and leucocyte counts, haemoglobin concentrations and haematocrit values. Plasma levels of glucose, free fatty acids, urea and P, and serum alanine aminotransferase and aspartate aminotransferase were not affected by bST treatment, and acetone was not detected. No adverse effects of bST on general health, infection status of mammary glands, mastitis incidence and reproduction were found.
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PMID:Effect of methionyl bovine somatotropin in a prolonged-release vehicle on milk production, hormone profiles and health in dairy cows. 145 34

The determination of ammonia in plasma, using glutamate dehydrogenase, is complicated by non-specific oxidation of the coenzyme, promoted by components of the sample matrix. Measurements performed with appropriate plasma blanks show that 2'-phosphorylated coenzymes (NADPH, deamino-NADPH) are much less oxidized than NADH. By adding lactate dehydrogenase, NADH oxidation by endogenous pyruvate can be completed within a short time. Considerable consumption of coenzyme occurs, however, and endogenous L-alanine aminotransferase also represents a possible source of interference. The results of ammonia determinations using deamino-NADPH (y) or NADPH (x) were identical (a = 0.0 mumol/l, b = 1.00; r = 0.996, n = 62). With NADH as the coenzyme, the method displays adequate specificity only at high sample dilution, e.g. in the measurement of urea after conversion to ammonia.
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PMID:Which is the appropriate coenzyme for the measurement of ammonia with glutamate dehydrogenase? 145 16

Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.
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PMID:Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats. 146 50

Gentamicin treatment caused an elevation in serum urea and creatinine concentrations and ALT activity, associated with pathological changes in the liver and kidney. The pathological and blood chemistry changes were more severe in diabetic gentamicin-treated than in non-diabetic gentamicin-treated rats. Alloxan-diabetic rats had lowered blood glutathione concentrations which may have been responsible for the enhancement of gentamicin toxicity in these rats.
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PMID:Comparison of gentamicin toxicity in normal and diabetic rats. 147 82

Biochemical and metabolic indicators were monitored in a group of volunteers suffering from a variety of chronic illnesses participating in a week's course on a special uncooked vegetable diet, known as "living food". Unmatched healthy controls ate the same diet cooked for 2 min in a microwave oven. After 1 week on the regimen, serum protein and urea contents decreased and alanine aminotransferase (ALAT) activity increased in both groups, although all within the normal range. Blood glucose increased in both groups to slightly above normal limits but total serum cholesterol dropped about 1 mmol/l from normal starting levels. Serum tocopherol and retinol increased only in the group eating the uncooked diet. In both groups urinary sodium dropped drastically without a significant change in potassium. Serum and urinary phenol and p-cresol diminished also significantly. It is concluded that this vegetable diet may be of some benefit in the short term but any longer-term use requires evaluation.
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PMID:Effects of eating an uncooked vegetable diet for 1 week. 148 62

Nineteen hematological and serum biochemical values were analyzed for 91 healthy cats of both sexes (aged 1 to 48 months) that were bred and reared in our laboratory. Age-related changes were found for many parameters. Red blood cell counts (RBC), hemoglobin (Hb), hematocrit (Ht), Mean corpuscular constants, GPT, total protein (TP) and albumin (ALB) initially were low but increased then stabilized. White blood cell counts (WBC), alkaline phosphatase (ALP), inorganic phosphorus (Pi), total bilirubin (TBil), total cholesterol (TC), glucose (GLU), and triglyceride (TG) initially were high, but decreased then stabilized. No age-related changes were found for GOT, blood urea nitrogen, or calcium. Of the parameters that changed with age, the mean corpuscular constants, GPT, GLU, and TG became stabilized during the first 3 to 4 months of life, but others (RBC, Hb, Ht, TP, ALB) became stabilized after 9 to 11 months, during which period body weight reached a plateau. Some parameters (WBC, ALP, TG, Pi) showed change up to 18 months of age. These results suggest that cats 9 to 11 months old can be regarded as adults; but for some parameters, cats aged 18 months, or older, are better regarded as adults. Sex-related differences in the values for mean corpuscular volume, mean corpuscular hemoglobin, and WBC that were found after 11 months of age were higher in females. ALB was higher in males.
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PMID:[Age-related changes in hematological and serum biochemical values in cats]. 150 20

Serum chemistry values were obtained from 64 adult San Joaquin kit foxes (Vulpes macrotis mutica) in western Kern County, California (USA). The goal of the study was to establish normal chemistry values for this endangered species. No significant differences were found for mean values of alanine aminotransferase (217.1 IU/l), alkaline phosphatase (44.2 IU/l), cholesterol (145.6 mg/dl), total protein (5.8 g/dl), creatinine (0.63 mg/dl), calcium (8.2 mg/dl), albumin (3.0 g/dl), glucose (129.2 mg/dl), amylase (196.8 IU/l), sodium (153.7 mEq/l) and phosphorus (5.42 mg/dl) between sexes or seasons. Significant differences were noted for aspartate aminotransferase, blood urea nitrogen and potassium between seasons. Possible disturbances in normal hepatic and renal functions were noted.
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PMID:Serum chemistry values of the endangered San Joaquin kit fox (Vulpes macrotis mutica). 151 73

Groups of 20 rats and 20 mice of each sex were administered monochloroacetic acid (MCAA) once daily, 5 days per week, in water by gavage for up to 13 weeks. Doses used were 0, 30, 60, 90, 120, or 150 mg/kg for rats and 0, 25, 50, 100, 150, or 200 mg/kg for mice. Compound-related deaths occurred at the four highest dose levels in rats and at the highest dose level in mice. Mean body weights of treated groups of rats and mice surviving until the end of the study were similar to those of the controls. A dose-related increase in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, as well as a dose-related increase in the relative liver and kidney weights was observed in rats but not in mice. A dose-related increase in the incidence and severity of cardiomyopathy occurred in rats. This lesion may be related to the inhibition of heart mitochondrial aconitase activity. No compound-related lesions were observed in mice. The results of this study indicate that F344 rats are more sensitive than B6C3F1 mice; sexes within the species were equally sensitive. The no-observable-effect level was estimated as 30 mg MCAA/kg body weight for rats and 100 mg MCAA/kg body weight for mice.
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PMID:Toxicity of monochloroacetic acid administered by gavage to F344 rats and B6C3F1 mice for up to 13 weeks. 153 74


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