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)

Rats (Sprague-Dawley) and mice (Balb/c) were given microcystin LR intraperitoneally and were killed at intervals up to 24 hr (rats) or 90 min (mice) and necropsied. The lowest consistently lethal dose was 160 micrograms/kg in rats and 100 micrograms/kg in mice. Rats that were clinically unaffected had no lesion. All clinically affected rats in all dose groups died (from 20 to 32 hr after toxin) and had similar hepatic lesions. Livers were enlarged and dark red beginning 40 to 60 min after toxin. Mild disassociation and rounding of centrilobular hepatocytes developed within 20 min. By 60 min after toxin, degeneration and necrosis of hepatocytes involved most of the lobules except for small periportal zones. Weights of livers and kidneys were significantly increased. Eosinophilic fibrillar material filled renal glomerular capillaries as early as 9 hr after toxin. At 18 to 24 hr there was moderate vacuolation of proximal tubular epithelium with mild tubular dilatation. Beginning at 1 hr, intact hepatocytes and hepatic debris were present in pulmonary vessels. Analysis of serum revealed an increase in alanine aminotransferase 40 min after toxin; at 6 to 12 hr there were significant increases in alkaline phosphatase, total bilirubin, blood urea nitrogen, and creatinine. Mice survived only 60 to 90 min after toxin. Hepatic lesions were similar to those in rats, but renal and pulmonary lesions were not seen.
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PMID:Toxicity of microcystin LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa, to rats and mice. 250 16

Changes in body weight gain and in biochemical parameters of blood and liver were assessed in Sprague-Dawley rats after multiple oral administration of three test doses of an Alberta crude oil (ACO). Rats treated with ACO (1.25-5 ml/kg) did not show statistically significant (p greater than .05) differences from control, corn-oil treated (5 ml/kg) rats, in body weight gains, liver weight, and blood biochemical indicators of liver (alanine aminotransferase, gamma glutamyltransferase), kidney (blood urea nitrogen, creatinine), and erythrocyte (adenosine 5'-triphosphate, 2,3-diphosphoglyceric acid, reduced glutathione) cytotoxicity. Treatment with ACO, however, caused statistically significant (p less than .05) and dose-related increases from control in (1) microsomal protein and cytochrome P-450 content, and NADPH-cytochrome c reductase, aryl hydrocarbon hydroxylase (AHH), and 7-ethoxycoumarin-O-deethylase (7-ECOD) activities, and (2) cytosolic glutathione transferase activity of liver. The induction of hepatic cytochrome P-450 and xenobiotic-metabolizing enzymes in microsomes of ACO-treated rats was probably associated with dose-related changes in isozymic forms of cytochrome P-450, as evidenced by (1) appearance of a 448-nm spectral peak in microsomes of ACO-treated rats and (2) differences in the inhibition pattern of AHH and 7-ECOD activities in microsomes of control and ACO-treated rats upon treatment with metyrapone and 7,8-benzoflavone.
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PMID:Induction of hepatic cytochrome P-450 and xenobiotic metabolizing enzymes in rats gavaged with an Alberta crude oil. 257 35

In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease in p-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2 x MELD(10) (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i.e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.
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PMID:Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat. 259 97

Cardiac output (CO), renal blood flow (RBF) and hepatic blood flow (HBF) were measured by the microsphere method before (control) and at 4 and 10 h after the induction of acute renal failure by intramuscular injection of glycerol in water-drinking, long-term saline-drinking and long-term captopril (converting enzyme inhibitor)-drinking rats. At 4 h after glycerol injection, CO, RBF and HBF significantly decreased in all three groups. At 10 h after glycerol injection, CO, RBF and HBF recovered to 88% of the respective control levels in only the saline-drinking rats, whereas CO, RBF and HBF further decreased to 53, 38 and 58% of the control levels, respectively in the captopril-drinking rats. At this time, not only acute renal failure but also hepatic disorder developed in the water-drinking and captopril-drinking rats as indicated by elevations of serum creatinine, urea nitrogen, alanine aminotransferase and other blood chemistry levels. The development of acute renal failure was not suppressed by captopril, but by long-term saline load. Thus, we conclude that the decrease in CO is an important variable of the early decrease in renal and hepatic perfusion in glycerol-induced acute renal failure, and that the early recovery of HBF as well as RBF may play an important role in preventing the development of acute renal failure.
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PMID:Cardiac output, renal blood flow and hepatic blood flow in rats with glycerol-induced acute renal failure. 260 3

Water purification generates a variety of chlorinated contaminants, one of which is dichloromaleic acid (DCMA). Exposure to this compound is likely to occur in combination with other drinking water pollutants, some of which are hepatotoxic. This study was designed to examine the interactive effects of carbon tetrachloride (CCl4), a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA (200-400 mg/kg, ip) caused modest dose-dependent increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and plasma urea nitrogen, as well as a marked depletion of nonprotein sulfhydryls (NPSH) in the liver, but not the kidney, by 24 hr. Pretreatment with inducers (phenobarbital or 3-methylcholanthrene) or an inhibitor (SKF 525A) of cytochrome P-450 activity failed to alter the response observed with DCMA alone. Alterations in 24-hr urine volume, osmolality, and water consumption also were observed. DCMA-mediated changes in plasma urea nitrogen and NPSH were reduced in magnitude with coadministration of CCl4 (1 ml/kg, ip), while anticipated CCl4-induced increases in ALT and AST were reduced with coexposure to DCMA. Renal slice experiments indicated that DCMA-treated rats were less able to accumulate the organic anion p-aminohippurate (PAH), whereas DCMA had no effect on accumulation of the organic cation tetraethylammonium (TEA). The combination of CCl4 and DCMA produced only additive effects on organic ion accumulation. These results suggest hepatic interaction possibly related to the metabolism of CCl4 and DCMA, resulting in renal and hepatic toxicity diminished from that observed with exposure to either agent alone.
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PMID:Effect in the rat of the interaction of dichloromaleic acid and carbon tetrachloride on renal and hepatic function. 261 81

The organ distribution and toxicity of p-DCB were compared in rats after either inhalation or oral administration. Male F344 rats were exposed to 500 or 125 ppm for 24 hr in a whole body inhalation chamber (H and L groups) or received a single dose of 300 mg/kg by gavage (PO group). The concentrations of p-DCB in the serum, liver, kidney and fatty tissues were measured by gas chromatography at intervals during and up to 24 hr after the treatment. Peak serum values for the L and H groups were lower than in the PO animals, but the organ/serum distribution ratios of p-DCB tended to be higher, in some cases markedly, in rats receiving the inhalation treatment. Significant increases in the levels of blood urea nitrogen, hepatic glutamic oxaloacetic transaminase and glutamic pyruvate transaminase and significant decreases in the levels of serum total cholesterol were observed only in the inhalation groups. Microscopically, the appearance of numerous eosinophilic droplets, together with swelling and desquamation of the proximal tubular epithelium of the kidney was especially noteworthy in H and L p-DCB treated groups. Thus, both biochemical and histopathological abnormalities induced by p-DCB were more pronounced in rats administered the compound by the inhalation route.
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PMID:Comparison of the toxicity of p-dichlorobenzene (p-DCB) administered to male F344 rats orally or by the inhalation route. 264 63

A veterinarian dealing with critical and trauma patients must be proficient with techniques for tracheostomy, thoracostomy tube placement for chest drainage, diagnostic peritoneal lavage, and autotransfusion. The utilization of these techniques may be life-saving in the critical patient. A tracheostomy is indicated in any patient with upper airway obstruction that cannot be managed with supplemental oxygen and/or orotracheal intubation. A tracheostomy tube with an inner cannula is preferred. Tracheostomy tubes should be cleaned at 3- to 4-h intervals, and methods should be employed to decrease thick tracheal secretions and to remove them from the trachea. A patient with a tracheostomy tube should be monitored continuously. A thoracostomy tube is indicated in any patient with large and/or continuous accumulation of air, blood, fluid, or chyle in the pleural space. The thoracostomy tube should be at least the same size as the patient's main stem bronchus. The thoracostomy tube is placed aseptically at the seventh intercostal space at the junction of the upper one third and lower two thirds of the lateral chest wall. Fluid or air may be removed from the chest intermittently with a three-way stopcock attached to the thoracostomy tube and a 60-ml syringe. If continuous drainage is needed, a continuous underwater seal and suction system should be used. Diagnostic abdominal paracentesis and peritoneal lavage are useful techniques in the determination of abdominal trauma, hollow viscus rupture, peritonitis, hepatic trauma, and urinary system trauma. When a multiholed catheter and lavage are used, the accuracy of detecting abdominal trauma is 95 per cent. When only needle paracentesis is used, the accuracy drops to 47 per cent. Abdominal lavage fluid can be analyzed for bacteria, whole blood, white blood cells, free bilirubin, creatinine, blood urea nitrogen, amylase, alkaline phosphatase, and alanine aminotransferase. Large volumes of whole blood recovered from abdominal or thoracic paracentesis can be reinfused into the patient if needed, providing it is not contaminated or markedly hemolyzed. The blood should be collected aseptically into blood bottles or bags. If the bleeding is ongoing or the blood only a few hours old, anticoagulants should be used. If the hemorrhage is several hours old, then clotting and defibrination has already occurred and the blood can be collected into "dry" bags or bottles. Before use, abdominal blood should be analyzed for urine, bile or fecal contamination. Blood collected from the thoracic cavity is much less likely to be contaminated. Autotransfused blood is administered through a standard blood administration set.
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PMID:Critical care surgical techniques. 268 82

The influence of selenium on cis-diamminedichloroplatinum(II) (c-DDP) nephrotoxicity in mice and rats was assessed, using single doses of both compounds. Sodium selenite, 2 mg of selenium per kg, given 1 h before c-DDP, greatly reduced blood urea nitrogen and creatinine levels and morphological kidney damage in both BALB/c mice and Wistar rats, while administration 1 h after c-DDP did not. Liver toxicity of selenium was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase and by routine histology. No liver damage was observed in animals treated with sodium selenite, 2 mg of selenium per kg, and physiological saline or c-DDP. Pretreatment with sodium selenite did not reduce the antitumor activity of c-DDP against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. The present results indicate that sodium selenite may provide protection against c-DDP nephrotoxicity, when it is given before c-DDP. Moreover, selenium has an antineoplastic activity against several tumors. The combination of these qualities may open new perspectives in cancer chemotherapy.
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PMID:Selenium-induced protection against cis-diamminedichloroplatinum(II) nephrotoxicity in mice and rats. 272 Jun 62

Groups of 21 male and 21 female Sprague-Dawley (SD) rats were fed diets containing pyriproxyfen at concentrations of 0, 80, 400, 2,000 and 10,000 ppm for 6 months. No death was found in any group. Alopecia in the neck and/or back, and soft feces were noticed in both sexes fed 10,000 ppm. A marked decrease in body weight gain was observed in both sexes fed 10,000 ppm throughout the treatment period, accompanying a decrease in food-consumption and an increase in water-intake during the initial stage of treatment. In terms of urinalysis, proteinuria, increases in K excretion, and, in number, yellowness or browish-yellowness in appearance, were observed in both sexes fed 10,000 ppm. In females fed 10,000 ppm, increases in bilirubin, Na excretion and specific gravity, and a decrease in ketone bodies, were observed. In hematology, decreases in erythrocyte count, hemoglobin concentration and hematocrit value, were observed in both sexes fed 10,000 ppm and in males fed 2,000 ppm. Also, an increase in MCH (in males), decreases in MCHC and platelet count (in females) were observed in 10,000 ppm group. Blood biochemistry revealed increases in total protein, albumin, alpha 2-globulin fraction, blood urea nitrogen, calcium (in both sexes fed 10,000 ppm), A/G ratio (in males fed 2,000 and 10,000 ppm), total cholesterol, phospholipid (in males fed 2,000 and 10,000 ppm, and in females fed 10,000 ppm), sodium (in females fed 2,000 and 10,000 ppm), gamma-glutamyl transpeptidase activity (in males fed 10,000 ppm) and alpha 1-globulin fraction (in females fed 10,000 ppm), and decreases in glucose, GOT (in both sexes fed 10,000 ppm), beta-globulin fraction (in males fed 2,000 and 10,000 ppm, and in females fed 10,000 ppm), GPT (in females fed 2,000 and 10,000 ppm), triglyceride, potassium (in males fed 10,000 ppm), and cholinesterase activity (in female fed 10,000 ppm). In organ weight, increases in liver (in males fed 2,000 ppm and 10,000 ppm, and in females fed 10,000 ppm), kidney (in both sexes fed 10,000 ppm) and thyroid (in females fed 10,000 ppm) and a decrease in pituitary (in females fed 2,000 and 10,000 ppm) were observed. Gross pathology revealed a higher incidence of blackish-brown coloration of the liver, and a lower incidence of accentuated lobular pattern of the liver (in males fed 10,000 ppm). An enlargement of the liver was seen in a few of both sexes fed 10,000 ppm. Histopathological examination showed that the sole effect attributable to treatment of this compound was on slight hypertrophy in the liver of both sexes fed 10,000 ppm, with a higher incidence.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[A six-month chronic dietary toxicity study of pyriproxyfen in rats]. 273 65

A new autoperfusion preparation was used to preserve six major organs simultaneously. In 7 Yorkshire white swine, the heart and lungs were separated and removed with the liver, pancreas, duodenum, and both kidneys en bloc while they were self-perfused. Fresh blood, glucose, electrolytes, heparin sodium, methylprednisolone, and a fat emulsion (Soyacal) were infused through the portal vein. No inotropic drugs were necessary. The organs survived for 18 to 37 hours (average survival, 24.6 +/- 2.7 hours [+/- standard error of the mean]). Aortic systolic pressure ranged from 78.5 +/- 5.5 to 98.7 +/- 11.8 mm Hg. Arterial oxygen tension ranged from 206 +/- 23 to 266 +/- 15 mm Hg and arterial carbon dioxide tension, from 20.1 +/- 2.7 to 32.1 +/- 4.9 mm Hg. Blood lactic acid levels decreased from 8.75 +/- 2.06 to 5.50 +/- 2.45 mmol/L at 24 hours. Urine output ranged from 25 to 82 mL/h. Blood urea nitrogen levels decreased from 9.17 +/- 0.59 to 4.67 +/- 1.08 mg/dL. Blood creatinine levels decreased from 1.34 +/- 0.10 to 0.57 +/- 0.22 mg/dL. Serum glutamicoxaloacetic transaminase levels increased from 73.4 +/- 26.3 to 194 +/- 179.5 U/L and serum glutamic-pyruvic transaminase levels, from 44.8 +/- 5.7 to 91 +/- 66.4 U/L. Red blood cell count ranged from 6.94 +/- 0.58 to 13.23 +/- 2.30 x 10(6)/microliters. Lung wet/dry weight ratios changed from 5.79 +/- 0.17 at the beginning to 6.25 +/- 0.16 at 24 hours. The technique for simultaneous multiorgan preservation presented here is simple, effective, and highly reproducible. This study appears to have produced one of the longest average survival times for autoperfusion.
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PMID:Eighteen to 37 hours' preservation of major organs using a new autoperfusion multiorgan preparation. 275 41


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