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)

To elucidate the possible toxicity of heavy metals in a renal tubular epithelial cell line derived from a normal cynomolgus female monkey (JTC-12, P3 (F], the effects of HgCl2, Na2CrO4 and NiCl2 on the dome formation and the release of intrinsic enzymes from the cells were studied. The results were as follows: 1. The JTC-12. P3(F) cells showed an evident dome formation when an inducer of differentiation (hexamethylene bisacetamide or N, N-dimethylformamide) was added to the medium. 2. Ouabain inhibited the dome formation of the JTC-12. P3(F) cells, suggesting that the dome formation is dependent on the active transepithelial transport of Na+. 3. The addition of 40 microM HgCl2, 10 microM Na2CrO4 or 20 microM NiCl2 inhibited the dome formation. 40 microM HgCl2, 10 microM Na2CrO4 or 150 microM NiCl2 caused significant cell death. 4. The addition of 5 microM HgCl2, 1 microM Na2CrO4 or 20 microM NiCl2 resulted in an increased release of lactate dehydrogenase into the medium for 6 hours. 20 microM HgCl2, 1 microM Na2CrO4 or 20 microM NiCl2 increased the medium gamma-glutamyl transpeptidase concentration for 6 hours, but 40 microM HgCl2, 5 microM Na2CrO4 or 100 microM NiCl2 did not cause a significant increase in the medium alkaline phosphatase concentration. The results suggest that the JTC-12. P3(F) cells possess, at least in part, functional characteristics similar to the other kidney proximal tubular cells and that the inhibition of dome formation and enzyme release from the cells may be the early indicators that predict metal toxicity to the cells.
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PMID:[Application of renal epithelial cell culture in study of organ toxicity of heavy metals]. 279 95

Previous experiments indicated that the partial reversal of mercuric chloride-induced renal dysfunction in rats by subsequent dithiothreitol (DTT) administration was not related to increased mercury excretion, decreased renal mercury concentration, a change in renal cortical subcellular mercury distribution, or the formation of a Hg-DTT complex. The present studies investigated whether DTT, a sulfhydryl reducing agent, protected renal cortical sulfhydryl status in general, or the activity of various renal enzymes (Mg- and Na,K-ATPases, alkaline phosphatase, and glutathione peroxidase) in particular. Additionally, the occurrence of conjugated dienes was used to assess the degree of lipid peroxidation. HgCl2 produced significant decreases in renal cortical protein-bound sulfhydryl concentration, alkaline phosphatase activity, and ATPase activity within 2.5 h of administration, with no effect observed on glutathione peroxidase activity or the levels of conjugated dienes in rat renal cortex. Administration of DTT 60 min after mercury neither provided protection from inhibition nor promoted restoration of the affected enzymes or sulfhydryl status. It is concluded that the partial protection of renal function offered by DTT in the early stages of mercury toxicity does not result from maintaining the integrity of renal cortical sulfhydryl status or the activity of the enzymes investigated. Furthermore, the early stages of mercury toxicity did not appear to be related to lipid peroxidation.
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PMID:Enzyme activity and sulfhydryl status in rat renal cortex following mercuric chloride and dithiothreitol administration. 284 77

Alterations in the levels of selected enzymes have been studied in the liver, kidney and brain of mouse following mercuric chloride (1 mg/Kg body wt./d) administration for 10, 20 and 30 d. The activity of acid phosphatase increased in all the tissues, the highest increase was recorded in the kidneys which showed as much as 4.5 fold elevation following mercuric chloride administration for 30 d. Although the alkaline phosphatase activity in the liver and the brain increased following HgCl2 administration, the kidneys experienced a tremendous decline in this enzyme following the same treatment. Mercury-induced changes in ATPase were complex inasmuch as the nature and magnitude of these changes varied with the tissue as well as the duration of the treatment. Whereas the liver ATPase declined after all the treatment intervals, this enzyme increased in the kidney and brain following administration of HgCl2 for 10 d. However, both the kidneys and brain registered a substantial fall in ATPase activity when HgCl2 administration was continued for 30 d. The levels of both glucose-6-phosphatase and succinic dehydrogenase decreased in all the tissues following HgCl2 administration. Invariably, the magnitude of decrease was the highest after 30 d treatment with HgCl2.
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PMID:Enzyme changes in the brain, liver and kidney following repeated administration of mercuric chloride. 302 11

In order to establish sensitive methods of detecting minor renal damage, changes of enzymes, tubular cell counts, and creatinine in the urine were investigated in rats that had been given nephrotoxic chemicals. Daily administration of mercuric chloride (HgCl2) dose-dependently increased urinary excretions of lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), lysozyme (LZM), N-acetyl-beta-D-glucosaminidase (NAG), and acid protease together with increased counts of tubular cells in the urine. The increase in tubular cell counts and the change in urinary LDH isoenzyme profile preceded the changes in the other enzymes. Daily administration of gentamicin (GM) increased urinary excretions of LDH, GOT, LZM, NAG, acid protease and tubular cell counts in a dose-dependent manner, but did not increase gamma-glutamyl transpeptidase (gamma-GTP) and ALP excretions. The urinary isoenzyme profiles of LDH in rats treated with GM were different from those with HgCl2. The increase in acid protease excretion outlasted those in LDH and GOT in the high dose group. It was concluded that the severity of renal damage can be readily detected by periodic determinations of the following urinary parameters: tubular cell counts, LDH isoenzyme, acid protease, LZM and NAG, in addition to either LDH or GOT and one of the enzymes ALP, LAP or gamma-GTP. Furthermore, the site of renal damage can be presumed from these results.
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PMID:Urinalysis for detection of chemically induced renal damage (1)--Changes in urinary excretions of enzymes and various components caused by mercuric chloride and gentamicin. 344 39

A method has been developed for preparing primary monolayer cultures of postnatal rat kidney cortical epithelial cells. These cultures maintained differentiated cell functions and epithelial-like morphology for several days in culture. The presence of alkaline phosphatase and maltase was used to confirm the presence of cells from the renal cortex. The concentrations of these enzymes were maintained in culture until day 3, but had declined significantly by day 5. Similar patterns were observed with cytochrome P-450 and glutathione content, although their concentrations remained stable from day 3 to day 5. Mercuric chloride, cadmium chloride and acetaminophen were evaluated for nephrotoxicity in this culture system. Treatment with these compounds resulted in dose-dependent changes in cell morphology and in biochemical parameters such as lactate dehydrogenase leakage, alkaline phosphatase activity and cellular glutathione content. With this culture system, it was possible to detect the acute toxicities of compounds that produce varying degrees of renal injury. Further development of this kidney culture system may have value in detecting potential nephrotoxins and in studying their mechanisms of toxicity.
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PMID:Development of a primary culture system of rat kidney cortical cells to evaluate the nephrotoxicity of xenobiotics. 353 92

The protective effect of selenite, seleno-dl-methionine and biological selenium against the renotoxicity of mercury was tested in rats. As the source of biological selenium, the liver soluble fraction of rats given 60 mumoles/kg selenite 3 days before sacrifice was used. The aim of the experiments was to test whether protective efficiency follows the reported order of ability to form HgSe. Mercury was given subcutaneously in doses of 2.5, 5.0 and 7.5 mumoles/kg HgCl2 and selenium was given in equimolar doses at the same time as Hg2+. Liver soluble fraction, biological selenium or liver soluble fraction supplemented with selenite or seleno-dl-methionine were given orally, while in experiments without liver soluble fraction the two selenium compounds were given subcutaneously. Biological selenium was tested only at the two lower dose levels. Both biological selenium and seleno-dl-methionine decreased the urinary excretion of mercury in the first 48 h, but less so than selenite and only selenite decreased the renal content of mercury at the end of this period. Urinary alkaline phosphatase activity and plasma urea nitrogen at the 2.5 and 5.0 mumoles/kg dose levels decreased in the order of no selenium greater than biological selenium greater than seleno-dl-methionine greater than selenite. As the reported HgSe formation increases in the same order, the experiments support the role of HgSe formation in the protective effect. The degree of necrotic damage in the P2 and P3 regions of the proximal tubular cells increased in the same order as the biochemical indicators at the 5.0 and 7.5 mumoles/kg dose levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the protection given by selenite, selenomethionine and biological selenium against the renotoxicity of mercury. 366 17

The effects of mercuric chloride intoxication on the activities of acid and alkaline phosphatases and glucose-6-phosphatase in the hepatopancreas of a freshwater prawn Macrobrachium lamarrei (H. Milne Edwards) were determined after 24, 48, 72, and 96 hr. Mercuric chloride intoxication resulted in elevation of acid phosphatase and inhibition of alkaline phosphatase activities, but glucose-6-phosphatase activity was elevated up to 72 hr after which (i.e., after 96 hr of exposure) inhibition in the enzyme activity was noted at two higher concentrations. Alterations in the activities of these enzymes after mercuric chloride intoxication have been shown to adversely affect the general metabolism of the freshwater prawn.
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PMID:Mercuric chloride intoxication in freshwater prawn. II. Effect on phosphatases activity. 609 12

Intrarenal distributions of three enzymes, gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (Al-p) and leucine aminopeptidase (LAP) were determined using six segments of nephrons. These enzymes were localized only in the proximal tubule. Intra-proximal distributions of the enzymes, however, were not uniform. The order of each enzyme activity in three segments of the proximal tubule, S1, S2 and S3 was as follows: Formula: (See Text) With subcutaneous administration of HgCl2 (1.0 mg/kg/day), urinary excretions of all three enzymes were increased from the 1st to the 2nd day and then decreased to the control level. However, after intraperitoneal administration of gentamicin sulfate (40 mg/kg/day), only Al-p activity in urine was significantly increased on the 1st day. Because of the lack of increasing blood levels of these enzymes after treatment, increased urinary excretions of the enzymes probably originate from the kidney, particularly the proximal tubule. The prominently increased excretion of gamma-GTP and LAP after HgCl2 treatment means that HgCl2 might damage S2 and S3, because the excretory patterns of the three enzymes were similar to their distribution profiles in S2 and S3. On the other hand, the toxic action of GM may be localized in S1 portion, in which Al-p activity proved to be highest among the three enzymes.
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PMID:[Evaluation of nephrotoxic site in rat proximal tubule: intrarenal distributions of three enzymes and effects of mercuric chloride and gentamicin on their excretion into urine (author's transl)]. 610 61

The acute renotoxicity of HgCl2 and phenylmercuric acetate (PhHgAc) was compared at two intraperitoneal dose levels: 0.5 and 1.0 mg Hg/kg. There was no difference in the type of proximal tubular damage caused by the two mercurials, but 1.0 mg Hg/kg as PhHgAc produced approximately the same degree of damage as 0.5 mg Hg/kg as HgCl2. At the selected dose levels only HgCl2, but not PhHgAc increased the urinary excretion of alkaline phosphatase. At 12 and 24 h after PhHgAc the content of mercury was higher in blood and lower in the kidneys and urine than after the administration of equimolar doses of HgCl2. As the difference in the rectal mercury contents of HgCl2 and PhHgAc treated groups declined with time, difference in renotoxicity seems to relate only to renal mercury taken up within 24 h of administration. It is suggested that the slower renal extraction of mercury - as in regenerating kidneys (Tandon and Magos 1980) - was responsible for the lower degree of renotoxicity in phenylmercury treated rats.
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PMID:The comparative renotoxicology of phenylmercury and mercuric chloride. 621 15

The relative merits of a comprehensive series of contemporary methods for detection of acute nephrotoxicity were evaluated. Male Sprague-Dawley rats were given 0, 0.25, 0.5, 1.0, or 3.0 mg mercuric chloride (HgCl2)/kg body weight by ip injection. Indices of nephrotoxicity were examined 8, 24, 48, 72, and 96 h later. Alterations in urine osmolality, volume, and protein levels were seen within 24 h in response to 1 mg/kg or more of HgCl2. Administration of 0.5-3.0 mg/kg produced dose-dependent increases in urinary excretion of maltase activity and glucose by 24 h, the period of peak effect. There was no increase in maltase or alkaline phosphatase (AP) activity in the serum of these animals. Enzymuria was not apparent in rats that had marked elevations in serum AP, argininosuccinate lyase, and ornithine carbamyl transferase activities as a result of physical (i.e., dichlorodifluoromethane-frozen) or chemical (carbon tetrachloride-induced) damage of the liver. Morphological alterations, in the proximal tubular epithelium of perfusion-fixed kidneys from HgCl2-dosed rats, paralleled the changes in enzyme excretion with respect to time of onset and dose-effect. There was a dose-dependent inhibition of tetraethylammonium (TEA) and p-aminohippurate (PAH) uptake by renal cortical slices at 24 h. Interestingly, increases in uptake of TEA and PAH were seen 8 h after a 1-mg/kg dose. Clearance of inulin and PAH in vivo were altered at 8 h by 0.5 and 1 mg/kg. Marked depression of these functional indices was seen at 24 h, by which time blood urea nitrogen (BUN) levels were increased. The 0.5- and 1.0-mg/kg doses also produced time- and dose-dependent increases in intracellular Na+ content which were maximal at 24 h. These results illustrate the importance of using a combination of biochemical and functional tests to elucidate the sequence of events in the kidney following toxic insult. Nevertheless, some of the simpler, traditional techniques (e.g., histopathology, urinalyses, BUN) were sensitive and organ-specific, and should continue to be very useful in nephrotoxicity testing/screening.
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PMID:Assessment of functional, morphological, and enzymatic tests for acute nephrotoxicity induced by mercuric chloride. 622 7


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