Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histological studies showed that the administration of p-nitrophenylarsonic acid to rats resulted in renal tubular necrosis. The nephrotoxin was administered intraperitoneally and doses greater than 30 mg/kg were found to be fatal. The severity of the renal lesion depended on the amount of the nephrotoxin used. Elevated serum urea levels, urinary protein and volume were recorded over an 8-day period following the injection of the nephrotoxin. These changes were paralleled by an increase in the activity of lactate dehydrogenase, acid and alkaline phosphatase, N-acetyl-beta-glucosaminidase and beta-glucosidase in the urine. beta-Glycosidase activities increased in kidney homogenates, immediately after the injection of the nephrotoxin, but this eventually fell to well below the normal range. Subcellular fractions were prepared from sucrose homogenates by differential centrifugation and beta-glycosidases and cytochrome oxidase were used as enzyme markers. Only minor changes in the activity of cytochrome oxidase activity resulted from the administration of p-nitrophenylarsonic acid. One of the earliest indications of renal damage was a decrease in lysosomal latency. The activities of the lysosomal and soluble enzymes were elevated above normal during the first two days after the injection of p-nitrophenylarsonic acid, but they fell to values, significantly lower than normal, on the third day. The isoenzymic forms of beta-galactosidase, beta-glucosidase and N-acetyl-beta-glucosaminidase in normal and damaged kidneys were studied, using starch gel electrophoresis. The activities of both the lysosomal and the soluble forms of these enzymes decreased following the injection of the nephrotoxin, confirming the results obtained with whole homogenates. The relationship between the changes in renal enzyme activity and urinary enzyme excretion during the nephrotoxic process is discussed.
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PMID:Studies on the nephrotoxicity of p-nitrophenylarsonic acid: changes in rat kidney and urinary enzyme activities following the administration of p-nitrophenylarsonic acid. 21 43

A case of fatal viscerotropic Rocky Mountain spotted fever with virtual absence of cutaneous lesions was diagnosed at autopsy by specific immunofluorescent demonstration of Rickettsia rickettsii in spleen, kidney, epididymis and skin. The clinical presentation was that of insidious onset of fever, renal failure, hypotension, hyponatremia and obtundation over a 10 day period. The patient had respiratory insufficiency, hypocalcemia, increases in creatinine phosphokinase (CPK), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH), alkaline phosphatase, billirubin and serum phosphate, grand mal seizure, myalgia and unremitting shock with death occurring on day 12 of illness. Postmortem examination revealed severe vasculitis with interstitial nephritis and multifocal tubular necrosis, pericholangitis with bile stasis, glial nodules in the brain, multifocal rhabdomyonecrosis, interstitial pneumonitis and mild interstitial myocarditis. Risk factors which this patient shared with other patients with fatal Rocky Mountain spotted fever were failure to recognize a rash, failure to obtain a tick bite history, male sex, black race and age greater than 30 years.
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PMID:Fatal viscerotropic Rocky Mountain spotted fever. Report of a case diagnosed by immunofluorescence. 34 5

A single intraperitoneal injection of hexochloro-1 : 3-butadiene (HCBD) at 100 mg/kg or above produced renal tubular necrosis in the rat by 24 h. Histological examination of the kidneys indicated damage to the straight portion of the proximal tubules. Urinary analysis showed diuresis, increased proteinuria and an increase in the excretion of N-acetyl-beta-D-glucosaminidase, and alkaline phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only a mild increase in protein excretion was observed. Twenty-four hours after 200 mg/kg HCBD, i.p., there was a marked decrease in the glomerular filtration rate (inulin clearance) and in the clearance of the organic anion (p-aminohippuric acid, PAH) and the organic cation (tetraethylammonium bromide, TEA) by the kidney. HCBD did not affect the accumulation of PAH or TEA by renal cortical slices when added in vitro at a concentration up to 0.1 mM. However, a decrease in PAH, but not TEA accumulation, was seen in renal cortical slices from rats treated with HCBD 24 h previously. Mercuric chloride (HgCl2), a known nephrotoxin, was used as a positive control for these studies. HCBD appears to specifically damage the straight portion of the proximal renal tubule and thereby selectively damage the organic anion transport system.
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PMID:The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney. 53 62

Parenteral administration of iron nitrilotriacetate (FeNTA) to rats resulted in marked loss in body weight, and increases in liver/and kidney/body weight ratios. Fatalities, due to renal failure, depended on dosage and age of the animals, and were greater (70%) after a single large dose (12 mg iron) than after repeated smaller doses (30%). FeNTA administered subchronically gave rise to an increase in ethane exhalation, and to decreased liver glutathione peroxidase activity, and decreased cytochrome P-450 concentration and benzphetamine N-demethylase activity. It also resulted in severe renal tubular necrosis, with deposition of iron in the tubular cells and loss of brush border alkaline phosphatase activity, resulting in a dose-dependent diuresis, with increased urinary excretion of glucose, iron and lipid peroxidation products, and decreased urine creatinine concentration. NTA alone had none of these effects but slightly decreased the hepatic concentration of iron.
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PMID:Effects of acute and sub-chronic administration of iron nitrilotriacetate in the rat. 257 73

Sheep received a single intragastric dose of 0.5, 1.0, 1.5, or 2.0 mmol F-/kg. Mild signs occurred at 1.5 mmol F-/kg and the animals recovered 2 days later. With the 2.0 mmol F-/kg dose all animals showed dullness, anorexia, and mild diarrhea which decreased from the third day. Dose-related congestion of duodenum, liver, kidney, and lung was observed in all animals. For the two higher doses kidney degeneration and tubular necrosis were associated with glomerular inflammation. Serum fluoride had a dose-related increase and was still significantly elevated on Day 7 for sheep given doses higher than or equal to 1.0 mmol F-/kg. Serum calcium and glucose levels were significantly lowered for all doses on the first day and the decrease was dose-related. In sheep given 2.0 mmol F-/kg total proteins and sodium were significantly lowered, whereas potassium and urea were increased (p less than 0.05); alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were both lowered (p less than 0.01) on the first day and ALP was still lowered on Day 7. For the highest dose glutamate dehydrogenase (GDH) was increased on Days 1 and 7 and gamma-glutamyl transferase (GGT) was increased on Day 1 and lowered on Day 7. Diuresis was increased for the two higher doses in Day 3 or 4 following dosage. A dose-related increase of daily fluoride excretion occurred for all doses on Day 1 and fluoride excretion was still significantly elevated on Day 7 except for the lowest dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental acute sodium fluoride poisoning in sheep: renal, hepatic, and metabolic effects. 286 58

Acute renal failure was diagnosed by clinical, necropsy and histological criteria in 39 flocks (20 low ground, 13 hill and six marginal upland) in areas served by six veterinary investigation centres. Forty-eight lambs of 12 different breeds or crosses were investigated. The mean age of affected lambs was 38 days (range seven to 84 days); 21 lambs (44 per cent) were aged seven to 28 days, while only eight (17 per cent) were older than two months. Mortality in clinically affected lambs was almost 100 per cent, with no response to various treatments. Histological examination showed that 40 lambs (83 per cent) had nephrosis, while the rest had toxic tubular necrosis, interstitial nephritis or tubular damage associated with oxalate crystal deposits. Only about half of the lambs had any evidence of enteric infections or enteropathy. Acutely ill lambs had azotaemia, haemoconcentration and proteinuria; some lambs had glycosuria or haematuria. Samples of plasma from 22 lambs with nephrosis were compared with similar samples from 82 incontact but asymptomatic lambs. The clinically affected group had significantly elevated plasma urea, creatinine, total protein, globulin, phosphorus and chloride concentrations and significantly reduced plasma calcium concentrations compared with healthy lambs. Affected lambs had a significant reduction also in the calcium:phosphorus ratio. No significant differences between groups was found in plasma concentrations of albumin, glucose, lactate, glycerol, creatine kinase, alkaline phosphatase, sodium, potassium or magnesium.
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PMID:Acute nephropathy in young lambs. 291 11

Male Porton-Wistar rats, 32 weeks old, were given i.p. one of the following doses of HgCl2; 0.5, 1.0 or 1.5 mg Hg/kg. In the preceding 4-week period and throughout the experiment the animals had free access to either tap water or 1.0% saline. The urinary excretion of alkaline phosphatase measured in urine samples, collected during the first 24 h after treatment with mercury, indicated that chronic saline loading significantly attenuated tubular damage caused by 0.5 mg or 1.0 mg Hg/kg, but not by 1.5 mg Hg/kg. Tubular necrosis 12 and 24 h after mercury was also less severe and extensive in saline than in tap water-drinking rats. This difference was still noticeable 4 days after mercury treatment in rats dosed with 0.5 mg Hg/kg, but death in the two higher dose groups prevented further pair-to-pair histological comparison. At the selected dose levels chronic saline loading did not decrease renal mercury content at 12 or 24 h and therefore protection was not associated with decrease in renal mercury uptake. The experiment indicates that chronic saline drinking, which at higher doses attenuates HgCl2-induced acute renal failure but not tubular necrosis, is able to moderate the severity of tubular necrosis when the dose of HgCl2 is as low as 0.5 mg Hg/kg. This protective effect diminishes as the dose is increased.
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PMID:Effect of prolonged saline loading on HgCl2-induced renal tubular damage. 648 35

Subacute toxicity study of fenvalerate was carried out in broiler chicks after oral administration @ 525.6 mg/kg once daily for 28 days. The blood concentration of fenvalerate following 1 day post-administration (pd) was 39.65 +/- 2.67 micrograms/ml and maintained plateau thereafter up to day 21 pd, and then declined (18.46 +/- 1.47 micrograms/ml) on day 28 pd. Intestine contained maximum residue (7.46 +/- 1.96 micrograms/g) followed by fat (5.95 +/- 1.16 micrograms/g), brain (5.06 +/- 0.96 micrograms/g), liver (3.93 +/- 0.51 micrograms/g), kidney (3.79 +/- 0.72 micrograms/g) and heart (1.72 +/- 0.35 micrograms/g). Histopathological examinations showed focal areas of necrosis in liver, proliferation and fibrosis of bile duct, larger size of glomeruli, glomerular and tubular necrosis in treated birds. Fenvalerate significantly increased the cholesterol level in brain, GPT activity in liver and heart, GOT activity in heart, and alkaline phosphatase activity in heart and brain tissue. It significantly decreased the glycogen content in liver and heart, GOT activity in brain and acid phosphatase activity in all the tissues analyzed. It appears that comparatively fowl is resistant to fenvalerate toxicity.
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PMID:Subacute toxicity of fenvalerate in broiler chicks: concentration, cytotoxicity and biochemical profiles. 782 86

To identify possible hazards of combined exposure to chemicals with the same target organ, a 24-hr single dose experiment was carried out in which the renal toxicity of mercuric chloride, potassium dichromate, d-limonene and hexachloro-1:3-butadiene administered simultaneously was compared with the nephrotoxicity of the individual compounds, using a total of 11 groups each consisting of five 12-wk-old male Wistar rats. The dose levels used were based on the results of a range-finding study with the individual compounds in the same strain of rats kept under similar experimental conditions, and comprised the 'Minimum-Nephrotoxic-Effect Level' (MNEL) and the 'No-Nephrotoxic-Effect Level' (NNEL) of each of the four compounds alone and in combination. A group of vehicle-treated rats served as controls. At the MNEL of the combination, antagonism of effects was encountered, seen for example as less severely increased activity of gamma-glutamyl transferase in the urine. Synergism of effects was also observed, for example increased severity of renal tubular necrosis, and more markedly increased activity of urinary lysozyme, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-glucosaminidase. More importantly, however, at the NNEL of the combination no signs of impaired renal function or renal damage were observed, suggesting absence of both dose additivity and potentiating interaction at the tested subeffective levels of the individual nephrotoxicants.
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PMID:Acute (24 hr) toxicity of a combination of four nephrotoxicants in rats compared with the toxicity of the individual compounds. 809 45

3-tert-Butyl-4-hydroxyanisole and tert-butyl-hydroquinone (TBHQ) are antioxidants known to promote renal and bladder carcinogenesis in the rat, although the mechanisms of these effects are unclear. Because glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic, and because 2-tert-butyl-5-(glutathion-S-yl)hydroquinone [5-(GSyl)TBHQ], 2-tert-butyl-6-(glutathion-S-yl)hydroquinone [6-(GSyl)TBHQ], and 2-tert-butyl-3,6-bis-(glutathion-S-yl)hydroquinone [3,6-bis-(GSyl)-TBHQ] have been identified recently as metabolites of TBHQ in the male rat, we investigated the effects of these metabolites in the male rat. At the highest dose tested (400 micromol/kg,i.v.) 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ caused 2-fold increases in the urinary excretion of gamma-glutamyl transpeptidase and alkaline phosphatase, and pigments arising from the polymerization of metabolites were deposited in the kidney. 3,6-bis-(GSyl)TBHQ (200 micromol/kg) was the most potent of the GSH conjugates tested and produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, and glucose (2-, 2-, 22-, and 11-fold increases, respectively). Alterations in the biochemical parameters correlated with the degree of single cell and tubular necrosis in the S(3)-M segment of the proximal tubule, as observed by light microscopy. In addition to nephrotoxicity, 3,6-bis-(GSyl)TBHQ increased the bladder wet weight 2-fold and caused severe hemorrhaging of the bladder. The half-wave oxidation potentials of 5-(Gsyl)TBHQ and 6-(GSyl)TBHQ were similar to that of TBHQ, whereas the half-wave oxidation potential of 3,6-bis-(Gsyl)TBHQ was approximately 100 mV higher than that of TBHQ. The TBHQ-GSH conjugates also catalyzed the formation of 8- hydroxydeoxyguanosine, indicating that GSH conjugation does not impair the redox activity of TBHQ. Because some chemicals may induce carcinogenesis by a mechanism involving cytotoxicity followed by sustained regenerative hyperplasia, our results suggest that the toxicity of GSH conjugates of TBHQ to kidney and bladder may contribute to the promoting effect of 3-tert-butyl-4-hydroxyanisole and TBHQ in these tissues.
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PMID:Glutathione conjugates of tert-butyl-hydroquinone, a metabolite of the urinary tract tumor promoter 3-tert-butyl-hydroxyanisole, are toxic to kidney and bladder. 864 Jul 54


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