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

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Time- and dose-dependent correlations of monochlorobenzene (CB) hepatotoxic effects were studied in view of (1) assumed mechanistic similarities to bromobenzene (BB), (2) the paucity of these data for CB, and (3) the relatively greater environmental importance of CB compared with BB. An ip dosage of 9.8 mmol/kg CB (approximately equal to LD10) produced evidence of liver toxicity over a 72-hr time course. Sulfobromophthalein (BSP) retention was maximized 3-16 hr post-treatment and normalized after 72 hr, whereas plasma alanine aminotransferase activity (ALT) and morphological evidence of damage were maximized about 48 hr after dosing. Maximal covalent binding to liver protein (3.07 nmol/mg) had occurred by 24 hr and approximately 36% of the administered dose had appeared in the urine by 48 hr. Liver and plasma CB concentrations were proportionally increased over the dosage range 2.0-14.7 mmol/kg but marked centrolobular necrosis and ALT elevations were seen only at the two highest dosages (9.8 and 14.7 mmol/kg). On the other hand, all doses depressed hepatic glutathione (GSH) to between 30 and 40% of control by 4 hr. Evidence of rapid recovery was evident at 2.0 and 4.9 mmol/kg but GSH levels remained low through 8 hr after 9.8 or 14.7 mmol/kg. Liver/body weight ratios were increased to a similar extent at all dosages when measured 24 hr post-treatment. Urinary excretion ranged from 59% at the low dosage to only 19% at the highest dosage by 24 hr. Dose-related covalent binding to liver protein at 24 hr occurred up to 9.8 mmol/kg but the binding associated with 14.7 mmol/kg was equivalent to that seen with the 4.9 mmol/kg dosage (1.6 nmol/mg protein). Cytochrome P-450 levels were depressed to between 50 and 80% of control 24 hr post-treatment with no clear dose relationship. While the hepatotoxic effects of CB and BB appear similar, these data suggest that some mechanistic differences are involved.
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PMID:Temporal and dose-response features of monochlorobenzene hepatotoxicity in rats. 398 88

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, alpha, beta and gamma-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, alpha value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and alpha values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.
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PMID:Function of reticuloendothelial system on CCl4 induced liver injury in mice. 409 93

Serum alanine aminotransferase activity was measured in 78 women before and after 1-6 months of continuous treatment with .5-mg norethindrone and in 98 women before and after 1-6 months of treatment with .5-mg chlormadinone acetate. 2-hour sulphobromophthalein (BSP) retention was performed on 3 and 11 women taking .4- and .5-mg norethindrone, respectively, and on 19 women taking chlormadinone acetate. There were no significant differences (p more than .05) between before and after aminotransferase activities. All BSP retention tests, except for 1 woman who took chlormadinone acetate, were normal. It is concluded that low doses of norethindrone and chlormadinone acetate have a low tendency to influence liver function as compared with combined oral contraceptives.
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PMID:The serum alanine aminotransferase activity and the two-hour sulphobromophthalein retention test during daily low-dose gestagen oral contraceptive treatment. 419 36

Effects of cianidanol on chronic liver injury induced by prolonged administration of carbon tetrachloride (CCl4) and on liver regeneration after partial hepatectomy of normal liver and CCl4 chronically injured liver were investigated by the measurement of plasma and liver biochemical parameters. Cianidanol increased the total plasma protein and 14C-Leu incorporation into plasma protein, while it reduced the contents of liver cholesterol and triglycerides. In rats with chronically injured liver or regenerating liver after partial hepatectomy of chronically injured liver, cianidanol improved the retention rate of BSP and the content of liver sugar. In rats with chronically injured liver, plasma GPT and GOT activities were reduced with the administration of cianidanol. Cianidanol had no effect on the regeneration rate after partial hepatectomy of normal liver, but it increased the regeneration rate after partial hepatectomy of chronically injured liver. These results suggest that cianidanol has the effect of improving the function of liver cells damaged by CCl4 treatment and of promoting the recovery of cell function to a normal level.
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PMID:[Effects of cianidanol on chronic liver injury induced by carbon tetrachloride and on liver regeneration after partial hepatectomy in rats]. 661 44

The effect of rolitetracycline (50 micrograms/g i.v.) alone or in combination with ethinylestradiol (0.1 and 1.0 micrograms/g s.c. once daily for 4 days) on liver function (BSP retention, serum GPT and SDH) and histomorphology was investigated in mice. Rolitetracycline alone increased liver weight, BSP-retention and serum GPT levels. Ethinylestradiol at the lower dose tended to enhance the BSP retention and the morphological changes of the liver produced by rolitetracycline but had no additional effect on the serum GPT and on liver weight. In contrast, hepatotoxic effects of the higher dose of ethinylestradiol were not further enhanced by rolitetracycline.
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PMID:Investigation into the combined hepatotoxicity of rolitetracycline and ethinyloestradiol. 662 65

Twenty mares were assigned to 1 of 4 groups: no altrenogest; altrenogest at 0.044 mg/kg BW; altrenogest at 0.132 mg/kg BW; or altrenogest at 0.220 mg/kg BW. Treatment was administered daily for 86 days. No signs of illness attributable to feeding altrenogest were observed during the trial. Treatment had no effect (P greater than .05) on the following parameters: WBC, differential WBC, platelet number, creatinine, LDH, CPK, total bilirubin, cholesterol, globulin, BSP, and erythrocyte sedimentation rate. When comparing values over time with pretreatment means or among treatment groups, there were differences (P less than .05) in RBC, PCV, Hb, ALT, PT, PTT, P, Na, TP, BUN, Cl and glucose. However, these changes remained within established normal ranges and also occurred in mares in the control group. There was no treatment by time interaction for any of these parameters. Treatment differences (P less than .05) were observed for K, Ca, alkaline phosphatase and AST during the course of the trial. However, only occasional values of these parameters were outside the established ranges. They were only slightly elevated and tended to be either sporadic or also occurred in control mares. Few of the observed changes could be attributed to the feeding of altrenogest.
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PMID:The effect of altrenogest, an oral progestin, on hematologic and biochemical parameters in mares. 668 30

The single intravenous administration of T-2 toxin to calves (0.25 mg/kg body weight) caused a marked decrease in the total peripheral white cell count which correlated with a decline in the neutrophil count. The circulating lymphocyte and platelet counts were unaffected by the toxin. A decline of approximately 10% occurred in hematocrit following toxin administration. A small transient increase was observed in serum aspartate aminotransferase, and lactate dehydrogenase activity together with a transient increase in the BSP retention test. There was no consistent pattern in the alteration of serum alanine aminotransferase activity and serum alkaline phosphate activity was unaffected by the toxin. The results suggest that in cattle the liver may not be the primary target organ for the cytotoxin effects of T-2 toxin.
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PMID:Effect of T-2 toxin on bovine hematological and serum enzyme parameters. 670 98

The hepatic involvement in Hodgkin's disease, histologically verified in 133 patients who underwent laparotomy or laparoscopy, proved to be singly related to the following clinical findings: result of the liver isotopic scan, liver and/or spleen enlargement, serum albumin less than or equal to 3.5 g/dl, GOT and/or GPT greater than or equal to 20 mU/ml, serum alkaline phosphatase (SAP) greater than or equal to 210 mU/ml, BSP retention at 45 min greater than or equal to 6.5% and ESR greater than or equal to 51 mm at 1 hr. Such clinical findings were jointly evaluated and further selected by means of a logistic discriminant analysis, and the simplest function with the best discriminant ability between involved and non-involved liver was made by liver scan, spleen enlargement, BSP retention and GOT (89.5% of correct diagnoses). Since the Ann Arbor clinical criteria for liver involvement showed correct diagnoses in 69-80% of the cases, more reliable criteria can be proposed. So, liver involvement is highly probably (a) when three or more of the five variables indicated above are abnormal, or (b) when a markedly abnormal liver scan is associated with alteration of at least one of the other four parameters: otherwise liver will be non-involved.
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PMID:New clinical criteria for the assessment of liver involvement in Hodgkin's disease. 689 25

Induction of endotoxin tolerance in rats led to reductions in bile flow and BSP excretion. BSP serum retention or storage of BSP in the liver was not affected. Although serum alanine aminotransferase (ALT) activity was slightly elevated in endotoxin-tolerant rats, the levels of serum aspartate amino-transferase (AST) and hepatic 5'-nucleotidase were normal. These in vivo data support the validity of in vitro studies demonstrating the cholestatic effect of endotoxin and the viewpoint that endotoxin may be responsible for the cholestatic jaundice associated with Gram-negative bacterial infections.
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PMID:Effects of endotoxin tolerance on hepatic excretory function: in vivo study. 704 30

In rats subjected to 90% jejunoileal by-pass or in sham-operated controls, liver function was compared to plasma nutritional state and adaptation of the intestine in continuity over a period of 3 months. While the plasma levels of GOT, GPT, and esterases A and C as cholinesterase C did not differ in either group, the percentage of retention of BSP increased until 8 weeks, then returned progressively to control values 12 weeks after small-bowel bypass. In contrast, plasma nonesterified fatty acid levels decreased significantly until 6 weeks, then recovered control values over the following periods. Plasma total protein and albumin levels also diminished after jejunoileal bypass, the most marked decrease being at the 4th postoperative week. The increase in villus size following the intestinal bypass was considered pronounced for the ileum between the 8th and the 12th week. These results suggest that BSP clearance is the most reliable criterion for hepatic dysfunction in the rat subjected to a jejunoileal bypass. In addition, the parallelism between the variations of BSP clearance, intestinal adaptation, and plasma nutritional state argue for the "nutritional" theory as the most probable explanation for the formation of hepatic lesions.
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PMID:BSP clearance as the most reliable criterion of hepatic dysfunction after jejunoileal bypass in the rat: arguments in favor of the existence of a pathogenetic mechanism involving a transient malnutrition state. 723 62


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