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N Asano

Publications and source records attributed to N Asano.

At least 73 records · Page 4Linked to original sources
PubMed1996

Two subsites on the active center of pig kidney trehalase.

A kinetic analysis of the active site of pig kidney trehalase was made by examining two types of inhibitors that are monosaccharide analogs and cause a competitive inhibition of the trehalase. Trehalase hydrolyzes trehalose (alpha-D-glycopyranosyl alpha-D-glucopyranoside) to give an equimolar mixture of alpha-D-glucose and, by inversion of configuration, beta-D-glucose. 1,4-Dideoxyl-1,4-imino-D-arabinitol is considered to be a transition state (glucosyl cation) analog, while methyl beta-D-glucoside, 1,5-dideoxy-1,5-imino-D-glucitol (1-deoxynojirimycin), fagomine, and 1-epivalidamine are considered to be analogs of the beta-D-glucose that is derived by hydrolysis of trehalose. These glucosyl cation inhibitor and beta-D-glucose analog inhibitors competed with each other at the same site on the active center of pig kidney trehalase and were therefore put together in one group (group A). Methyl alpha-D-mannoside and 1-deoxymannojirimycin were also competitive inhibitors of trehalase and competed with each other for the same site. However, an inhibitor in group A did not compete with the methyl alpha-D-mannoside or 1,5-dideoxy-1,5-imino-D-mannitol (1-deoxymannojirimycin). Thus these latter two inhibitors were placed in group B. These results support the hypothesis that the active center of trehalase may comprise two subsites, one for catalysis and one for recognition, that act separately on each of the glucose of the trehalose. The catalysis site requires the correct D-glucose configuration at carbons 2, 3, 4, and 5 or a good superimposition onto the glucosyl cation intermediate. The C2 equatorial OH group of a glucopyranosyl residue appears to be important for binding at the catalytic site since 1-deoxynojirimycin is more tightly bound by two orders of magnitude over its 2-deoxy derivative, fagomine. The beta-D-glucose and glucosyl cation analogs best fit this site. The recognition site is compatible with D-glucose and its analogs bearing the alpha configuration at the anomeric position. alpha-D-Mannose analogs are much more tightly bound than the corresponding D-gluco compound at this site. The extremely high affinity (Ki = 0.52 nM) of validoxylamine A, a mimic of the substrate in the transition state, derives from the synergistic interactions of two cyclitol units with two subsites. The value obtained by multiplying the Ki (1.2 microM) for 1-epivalidamine times that for 1-deoxymannojirimycin (Ki = 0.39 mM) is very close to that for validoxylamine A. The results described here may be applicable to other trehalase molecules.

Animals↗
PubMed1996

Changes in urinary enzyme activity and histochemical findings in experimental tubular injury induced by gold sodium thiomalate.

To elucidate the renal injury induced by gold treatment, we administered various doses of gold sodium thiomalate (GST) to Wistar rats and investigated alterations in the urinary enzyme activity, gamma-glutamyl transpeptidase (gamma GTP) and N-acetyl-beta-glucosaminidase (NAG) activity, and histochemical change of enzymes, gamma GTP, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in the renal tissue. The single administration of a large dose of gold salts induced acute tubular necrosis and enzyme leakage was detected histochemically without damage to the glomerulus. After chronic administration of small doses of gold salts, the urinary gamma GTP activities gradually increased, but urinary NAG activities did not. These findings suggested that the change in urinary enzyme activities, which leaked from inside of brushborder or lysosome, indicated the degree or localization of tubular damage, because renal tubules were selectively injured by gold salts.

Acetylglucosaminidase↗
PubMed1995

N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication.

The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from 1H NMR analyses, mainly using 3J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious loss of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC50 values of 69 and 49 micrograms/mL in MT-4 cells and 100 and 37 micrograms/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.

Alkylation↗
PubMed1995

Calystegins of Physalis alkekengi var. francheti (Solanaceae). Structure determination and their glycosidase inhibitory activities.

Five calystegins were extracted from the roots of Physalis alkekengi var. francheti (Solanaceae) with hot water and purified to homogeneity by the combination of a variety of ion-exchange column chromatographies. Their structures have been determined from the 1H- and 13C-NMR spectral data, and two of the compounds were identified as calystegins A3 and B2, which have been isolated from the roots of Calystegia sepium (Convolvulaceae). Two of the remaining three were found to be 1 alpha, 3 alpha, 4 beta-trihydroxy-nor-tropane and 1 alpha, 2 alpha, 3 alpha, 4 beta-tetrahydroxy-nor-tropane and given the trivial name calystegins A5 and B3, respectively. The last calystegin was assigned as 1 alpha, 2 beta, 3 alpha, 6 alpha-tetrahydroxy-nor-tropane, which was the same as the relative configuration proposed in the literature for calystegin B1 isolated from C. sepium. However, the 13C-NMR spectral data for the compound from C. sepium differed substantially from our results. From a personal communication with the authors of the original paper on calystegins, it was clarified that the 13C-NMR chemical shifts of calystegin B1 in the original paper had been erroneous. Since their corrected 13C-NMR data of calystegin B1 and its 1H-NMR chemical shifts in the original paper are very close to our present data, we concluded that both compounds from C. sepium and P. alkekengi are identical. Calystegin B2 has been known to be a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.2 microM) and coffee bean alpha-galactosidase (Ki = 0.86 microM). In this study calystegin B1 (1 alpha, 2 beta, 3 alpha, 6 alpha-tetrahydroxy-nor-tropane) proved to be a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.9 microM) and bovine liver beta-galactosidase (Ki = 1.6 microM), but not an inhibitor of alpha-galactosidases. Calystegin A3 was found to be a weaker inhibitor compared to calystegin B2 but with the same inhibitory spectrum. Calystegin A5, a 2-deoxy derivative of calystegin B2, showed no activity against any glycosidases tested. Since calystegin B3, a 2-epimer of calystegin B2, also exhibited only a weak inhibitory activity, it was concluded that the equatorially oriented OH group at C2 is the essential feature for recognition and strong binding by the active site of glycosidases.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaloids↗
PubMed1995

Ultrastructure of contusion cataract.

We investigated the histopathologic condition of four lenses with contusion rosette cataract by light and electron microscopy; periods between blunt trauma and cataract extraction varied from 4 months to 40 years. The initial morphologic changes appear to be the formation of intercellular vacuoles within the lens epithelium and the swelling of superficial cortical lens fibers. Signs of beginning fiber degeneration within the edematous zone include fragmentation of fiber cytoplasm into droplets and globules, formation of abnormal membrane arrangements, and enlargement of intercellular spaces. Late rosette opacities manifest as sharply demarcated layers of vacuolic degeneration in the deeper cortex. We suggest that in contusion cataract, a traumatically induced dysfunction of the lens epithelium leads to an edema of superficial cortical lens fibers that subsequently undergo degeneration and produce a localized and permanent lamellar zone of vacuolation. With time and with the formation of new clear lens cells, this layer becomes gradually compressed and displaced deeper into the cortex.

Aged↗
PubMed1995

Potentiating effects on pilocarpine-induced saliva secretion, by extracts and N-containing sugars derived from mulberry leaves, in streptozocin-diabetic mice.

The effects of hot water extracts and six compounds of N-containing sugars, 1-deoxynojirimycin (DNJ), N-methyl-DNJ (N-Me-DNJ), 2-O-alpha-D-galactopyranosyl-DNJ (GAL-DNJ), fagomine, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), and 1,2 alpha,3 beta,4 alpha-tetrahydroxynortropane (calystegin B2), derived from mulberry leaves (Morus alba L.), were investigated on pilocarpine-induced saliva secretion in streptozocin (STZ)-induced diabetic mice. The extracts (100 and 200 mg/kg, i.p.) significantly potentiated the pilocarpine-induced salivary flow but not the protein content. The component compounds (37.5-300 mumol/kg) potentiated the saliva secretion, and the potency order was DAB > fagomine > GAL-DNJ. Only fagomine significantly increased the protein content in the saliva. The potentiation of pilocarpine-induced salivary flow was correlated with anti-hyperglycemic effects by the extract and GAL-DNJ from mulberry leaves in the same dose ranges.

Amino Sugars↗
PubMed1995

Enhanced pressor response in spontaneously hypertensive rats induced by stimulation of vasopressin-V1 receptors.

To elucidate the effect of the arginine vasopressin (AVP) system in vivo, especially V1 and V2 activity, on blood pressure, we measured the acute changes in blood pressure and heart rate after AVP, OPC-21,268 (a V1 receptor antagonist), and OPC-31,260 (a V2 receptor antagonist) were injected intravenously in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of 15 weeks. Compared with the control period, single injection of AVP 5 ng/kg significantly increased systolic blood pressure in WKY rats without a concomitant increase in heart rate, but there was no significant increase in blood pressure in SHR. In contrast, single injection of either OPC-21,268 3 mg/kg or OPC-31,260 3 mg/kg did not affect blood pressure or heart rate in either SHR or WKY rats. Injection of AVP after the administration of OPC-31,260 induced a greater increase in blood pressure in SHR than in WKY rats, whereas injection of AVP after the administration of OPC-21,268 did not induce any clear increase in blood pressure in SHR or WKY rats. These results suggest that SHR have enhanced pressor activity mediated by V1 receptors and that this increase may be due to an increase in their number. In conclusion, enhancement of V1 activity may contribute to the development of high blood pressure in SHR.

Animals↗
PubMed1995

A histopathologic study of iris changes in pseudoexfoliation syndrome.

PURPOSE: To investigate the histopathologic causes for the most prominent clinical observations of the iris of patients with pseudoexfoliation syndrome (PXS), particularly poor mydriasis but also atrophy of the iris pigment epithelium with anterior chamber melanin dispersion, stromal atrophy, and vascular changes. METHODS: Thirty-three iris specimens from patients with PXS with and without glaucoma were investigated by transmission electron microscopy with special regard to sphincter and dilator muscle tissues. RESULTS: Pseudoexfoliation fibers were observed consistently in association with fibroblasts and melanocytes in the iris stroma, endothelial cells and pericytes of vessels, both anterior and posterior pigment epithelial cells, and muscle cells of sphincter and dilator muscles. The various cell types showed uniformly surface cell membrane excavations with PXS fibers, indicating local PXS production. Focal disintegration of the pigment epithelial layers was associated with unusual PXS material aggregations along the apical aspects of epithelial cells. Compared with age-matched control specimens, the muscle cells showed, in addition to PXS production, remarkable degenerative and atrophic changes in PXS eyes. CONCLUSION: The authors suggest that abnormal extracellular matrix production and/or vascular abnormalities leading to tissue hypoxia cause degenerative tissue changes and that atrophy of muscle cells might potentiate the reduction of dilating properties of the iris.

Aged↗
PubMed1994

Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases.

Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyranoses are 1-deoxynojirimycin (1), the D-manno (2), D-allo (3), and D-galacto (4) isomers of 1, fagomine (1,2-dideoxynojirimycin, 5), and the D-allo (6) and D-galacto (7) isomers of 5, while the three furanoses are 2,5-dideoxy-2,5-imino-D-mannitol (8), 1,4-dideoxy-1,4-imino-D-arabinitol (9), and 1,4-dideoxy-1,4-imino-D-ribitol (10). The 2-deoxygenation and/or 3-epimerization of 1 enhanced the potency for rat intestinal lactase and bovine liver cytosolic beta-galactosidase. Especially compound 6 showed a potent inhibitory activity against both enzymes, and compound 8, a mimic of beta-D-fructofuranose, was a potent inhibitor of both beta-galactosidases as well. Compound 4, which has been known as a powerful alpha-galactosidase inhibitor, exhibited no significant inhibitory activity for most of mammalian beta-galactosidases. In addition, compound 6 fairly retained a potency of 1 toward rat intestinal isomaltase. In this study, compound 8, known as a processing alpha-glucosidase I inhibitor in cell culture, has been found to have no effect on processing alpha-glucosidase II, whereas 9 has been shown to be a good nonspecific inhibitor of intestinal isomaltase, processing alpha-glucosidase II, Golgi alpha-mannosidases I and II, and porcine kidney trehalase. It has been speculated that glycosidase inhibitors have structures which resemble those of the respective glycosyl cations. This Broad inhibitory activity of 9 toward various glycosidases suggest that it superimposes well on the various glycosyl cations.

Animals↗
PubMed1994

N-containing sugars from Morus alba and their glycosidase inhibitory activities.

The reexamination of N-containing sugars from the roots of Morus alba by improved purification procedures led to the isolation of eighteen N-containing sugars, including seven that were isolated from the leaves of Morus bombycis. These N-containing sugars are 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), fagomine (3), 3-epi-fagomine (4), 1,4-dideoxy-1,4-imino-D-arabinitol (5), 1,4-dideoxy-1,4-imino-D-ribitol (6), calystegin B2 (1 alpha,2 beta,3 alpha,4 beta-tetrahydroxy-nor-tropane, 7), calystegin C1 (1 alpha,2 beta,3 alpha,4 beta,6 alpha-pentahydroxy-nor-tropane, 8), 1,4-dideoxy-1,4-imino-(2-O-beta-D-glucopyranosyl)-D-arabinitol (9), and nine glycosides of 1. These glycosides consist of 2-O- and 6-O-alpha-D-galactopyranosyl-1-deoxynojirimycins (10 and 11, respectively), 2-O-, 3-O- and 4-O-alpha-D-glucopyranosyl-1-deoxynojirimycins (12, 13, and 14, respectively), and 2-O-, 3-O-, 4-O- and 6-O-beta-D-glucopyranosyl-1-deoxynojirimycins (15, 16, 17, and 18, respectively). Compound 4 is a new member of polyhydroxylated piperidine alkaloids, and the isolation of 6 is the first report of its natural occurrence. It has recently been found that the polyhydroxy-nor-tropane alkaloids possess potent glycosidase inhibitory activities. Calystegin A3 is the trihydroxy-nor-tropane, and calystegins B1 and B2 are the tetrahydroxy-nor-tropane. Calystegin C1, a new member of calystegins, is the first naturally occurring pentahydroxy-nor-tropane alkaloid. The inhibitory activities of these compounds were investigated against rat digestive glycosidases and various commercially available glycosidases.

1-Deoxynojirimycin↗
PubMed1994

Enzymic synthesis of alpha- and beta-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities.

1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice alpha-glucosidase. Several glucosides of 1 were synthesized by use of the native and immobilized enzyme and their effect on various enzymes was investigated. Transglucosylation reactions using rice alpha-glucosidase, yeast alpha- and beta-glucosidases purified from Rhodotorula lactosa were performed with maltose or cellobiose as a glucose donor and N-(benzyloxycarbonyl)-1-deoxynojirimycin (2) as an acceptor. The transglucosylation reaction using native rice alpha-glucosidase afforded 3-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (4), 4-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (5), and 2-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (3) in yields of 40, 13, and 2%, respectively, after 30 min. The transglucosylation reaction using immobilized rice alpha-glucosidase was similar to that using the native enzyme. In the system using native yeast alpha-glucosidase, 3, 5, and 4 were formed in yields of 34, 13, and 6%, respectively, after 15 h. The immobilization of yeast alpha-glucosidase caused a significant decrease in transglucosylation activity. Yeast beta-glucosidase showed a high transglucosylation activity and incubation with the reaction system afforded 2-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (6) and 4-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (7) in yields of 69 and 3%, respectively, after 3 h. The transglucosylation reaction using immobilized yeast beta-glucosidase preferentially afforded 6 in a yield of 73% after 3 h. After removal of N-benzyloxycarbonyl group from the product glucosides, their glycosidase inhibitory activities were measured. 3-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (9) retained the potent inhibition of 1 against rat intestinal sucrase activity and was more effective than 1 against rice alpha-glucosidase. 4-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (10) retained the potency of 1 against rat intestinal sucrase and isomaltase. 2-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (8) was more effective than 1 against trehalases.

1-Deoxynojirimycin↗
PubMed1994

Sugars with nitrogen in the ring isolated from the leaves of Morus bombycis.

It is known that 1-deoxynojirimycin (1) is contained in the leaves and roots of Morus sp. The modified purification procedures of 1 from leaves of Morus bombycis led to the isolation of many polyhydroxylated alkaloids. These include 1, N-methyl-1-deoxynojirimycin (2), 2-O-alpha-D-galactopyranosyl-1-deoxynojirimycin (3), fagomine (4), 1,4-dideoxy-1,4-imino-D-arabinitol (5), 1,4-dideoxy-1,4-imino-(2-O-beta-D-glucopyranosyl)-D-arabinitol (6), and 1 alpha,2 beta,3 alpha,4 beta-tetrahydroxy-nor-tropane (7), designated nortropanoline. The isolation of 2 is the first report of its natural occurrence. Compounds 3 and 6 are the first naturally occurring glycosides of 1 and 5, respectively. Natural alkaloidal glycosidase inhibitors are classified into five structural types: namely polyhydroxylated piperidines, pyrrolidines, pyrrolines, indolizidines, and pyrrolizidines. Nortropanoline is a novel tropane alkaloid and a new type of polyhydroxylated alkaloid.

1-Deoxynojirimycin↗
PubMed1994

In vitro micro-autoradiography of atrial natriuretic peptide in biopsy specimens from patients with renal diseases.

We investigated the localization and density of atrial natriuretic peptide (ANP) receptors in human renal biopsy specimens by using in vitro micro-autoradiography (ARG) of [125I]-alpha-human (1-28) ANP. In a preliminary study, we measured the effect of storing tissue samples on ANP binding, using in vitro micro-ARG of Wistar rat kidney under optimal conditions. Duration of the preservation period did not affect ANP binding to renal tissue until samples had been stored at -30 degrees C for two years. A total of 11 human renal tissues were used to assay binding of ANP-ARG, including normal tissue obtained after nephrectomy because of renal cancer. ANP binding occurred predominantly within the glomerulus and, to a lesser extent, in the tubular region both in rat kidney sections and in human renal biopsy specimens. The density of ANP binding, calculated by counting grains in fixed areas, was compared with normal and pathological tissues. The density of grains tended to decrease in patients with renal dysfunction and hypertension except for one case of IgA nephropathy with normal renal function and blood pressure. The density of grains increased in a patient with nephrogenic diabetes insipidus. In the present study, we have established a method that uses in vitro micro-ARG for assessing ANP binding in human biopsy specimens.

Animals↗
PubMed1993

A time-dependent inactivation of aromatase by 19-substituted androst-4-ene-3,6,17-triones.

Diastereomeric (19S)- and (19R)-19-ethynyl-19-acetoxy derivatives of androst-4-ene-3,6,17-trione (AT) (9 and 10) and 19,19-difluoro AT (12) were synthesized. The 19,19-difluoro compound (12) was an effective competitive inhibitor of human placental aromatase with an inhibition constant (ki) of 1.8 microM but the acetylenic 9 and 10 were poor inhibitors of the enzyme with k(is) of 75 and 67 microM, respectively. Inhibitor 12 caused a time-dependent, biphasic loss of aromatase activity in the presence of reduced nicotinamide-adenine-dinucleotide phosphate (NADPH) in air, whereas the other two caused a time-dependent, pseudo-first-order inactivation of the activity with rate constants for inactivation of 0.250, 0.077, and 0.065 min-1 for steroids 12, 9, and 10. NADPH was required for the time-dependent inactivation, and the substrate androst-4-ene-3,17-dione prevented it. L-Cysteine did not protect aromatase from the inactivation.

Androstenes↗
PubMed1993

Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.

To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.

Adenocarcinoma↗
PubMed1993

Pulmonary carcinoma associated with hamartoma in an 11-year-old boy.

PURPOSE: We describe a poorly differentiated adenocarcinoma of the lung in an 11-year-old boy who had had a pulmonary hamartoma for at least 8 years. CONCLUSIONS: A hamartoma, even if clinically silent, may lead to the development of malignant tumors on rare occasions.

Adenocarcinoma↗
PubMed1992

Effect of synthetic protease inhibitors on superoxide (O2-), hydrogen peroxide (H2O2) and hydroxyl radical production by human polymorphonuclear leukocytes.

The effects of clinically used protease inhibitors (aprotinin, nafamostat mesilate, gabexate mesilate) on the production of oxygen-derived free radicals (O2-, H2O2, .OH) by human polymorphonuclear leukocytes were examined. Nafamostat mesilate and gabexate mesilate markedly and dose-dependently inhibited zymosan-stimulated O2- production by human polymorphonuclear leukocytes. However, aprotinin had a slight scavenging effect on O2- produced by the xanthine-xanthine oxidase system. All the protease inhibitors inhibited H2O2 production, but had no significant scavenging effect on H2O2. Nafamostat mesilate and gabexate mesilate slightly inhibited .OH production. These results indicate that the synthetic protease inhibitors nafamostat mesilate and gabexate mesilate inhibit the production of various activated oxygen radicals by human polymorphonuclear leukocytes, and the differences in their inhibitory effects suggest that each synthetic protease inhibitor is specific for a particular oxygen-derived free radical.

Adult↗