Studies on glucosaminidase. <i>N</i>-Acetyl-β-glucosaminidase in rat kidney

Pugh, Doreen; Leaback, David H.; Walker, P. G.

doi:10.1042/bj0650464

Cited by 123 publications

(32 citation statements)

References 6 publications

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“…The parameters tested included the release of lysosomal and cytoplasmic enzymes, as well as of a monokine, lymphocyte-activating factor (LAF (3)(4)(5)(6), also designated Interleukin 1 (7) Enzyme assays. l3-N-Acetylglucosaminidase (hexosaminidase) was determined by the method of Pugh et al (10). The assays were carried out in duplicate, with the means differing from the actual values by <15%.…”

Section: Introductionmentioning

confidence: 99%

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Gery¹,

Zigler²,

Ro³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Although the enzymatic lesion inGaucher's disease is well established, little is known concerning the pathogenic mechanisms involved in the clinical manifestations of the disease. In order to obtain insight into this unexplored aspect of Gaucher's disease, we examined the effects of glucocerebroside (GL1) at the cellular level in monolayers of cultured murine macrophages. The addition of GL1 to these cultures stimulated the macrophages to release increased amounts of lymphocyte-activating factor (LAF) and lysosomal enzymes into the medium. These responses were proportional to the amount of GL1 added to the culture. At higher levels of GL1 (.20 ,ug/ml), lactic dehydrogenase, a cytoplasmic enzyme was also released indicating cellular damage at these doses.Intracellular LAF also increased in macrophages incubated with the high doses of GL1, demonstrating an increase in total LAF production by these cells. Lipopolysaccharide acted synergistically with GL1 and stimulated the release of exceedingly high levels of LAF which had a molecular weight profile similar to that of LAF released by exposure to lipopolysaccharide alone. Unlike GL1, galactocerebroside, sphingomyelin, and ceramidetrihexoside, exerted little or no effect on the release of macrophage products. The effect of GL, was selective for macrophages since addition of this material to mouse lens epithelial cells had no detectable cytotoxic effect and it was only slightly toxic to lymphocytes or P815 cells in concentrations at which macrophages were clearly affected. A direct relationship was observed between the cytotoxicity of the sphingolipids and their accumulation in various cells. Macrophages accumu-

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Section: Introductionmentioning

confidence: 99%

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Gery¹,

Zigler²,

Ro³

et al. 1981

J. Clin. Invest.

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“…NAG was measured by the method of Pugh et al (33). The lack of AMB interference in NAG activity was verified in vitro.…”

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confidence: 99%

Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats

Longuet

Joly

Amirault

et al. 1991

Antimicrob Agents Chemother

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Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens.Systemic mycoses are a major cause of morbidity and mortality among immunocompromised patients (8,42,43). Although several new antifungal agents, particularly triazoles, have recently become available, amphotericin B (AMB) remains the most active drug for the treatment of opportunistic fungal infections (12,28). Its clinical use is limited by side effects, the most serious being nephrotoxicity. Harmful renal effects include inability to concentrate urine (1, 3, 4, 10), defective urinary acidification due to distal tubule dysfunction (10, 27, 31), renal potassium wasting (5), and depressed glomerular filtration rate (GFR) and renal plasma flow (6, 7).AMB toxicity was shown to be reduced when the drug was incorporated into liposomes or complexed with lipids (L-AMB), allowing higher doses to be infused and thereby increasing the efficiency of treatment in experimental fungal infections (23,36,37). However, the in vivo protective effect of liposomes (13, 38) or lipidic emulsions (18) against the experimental renal toxicity of AMB has been evaluated only after a single administration of the drug. Therefore, the experimental nephrotoxicity of L-AMB under conditions of repeated administration remains largely unknown. L-AMB has been used for the treatment of systemic mycoses in cancer patients with encouraging preliminary results (21, 22, 34), but again, the side effects on renal function have not been investigated in detail. Severe underlying disease, poor clinical conditions, previous treatment with free AMB, and multiple drug regimens might account for the difficulties encountered in evaluating renal function alterations in these * Corresponding author. patients. In ...

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“…phenolphthalein). In the case of /-N-acetylglucosaminidase assays, the homogenates, after incubation for 1 hour at 37°with 0.05 M citric acid buffer pH 4.3, followed by the addition of 0.15 M sodium chloride (Pugh, Leaback and Walker, 1957a), were centrifuged and the supernatant fractionated with saturated ammonium sulphate, the fraction precipitated between 20 and 80 per cent saturation being used for assay. This avoided the high enzyme blanks usually obtained with crude homogenates when estimating phenol.…”

Section: Method8mentioning

confidence: 99%

“…608 red filter in the absorptiometer. The conditions of assay were those described by Pugh, Leaback and Walker (1957b).…”

Section: Method8mentioning

confidence: 99%

Comparison of Different Glycosidase Activities in Conditions of Cancer

Conchie¹,

Levvy²

1957

Br J Cancer

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Studies on glucosaminidase. N-Acetyl-β-glucosaminidase in rat kidney

Cited by 123 publications

References 6 publications

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Selective Effects of Glucocerebroside (Gaucher's Storage Material) on Macrophage Cultures

Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats

Comparison of Different Glycosidase Activities in Conditions of Cancer

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