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At least 19 recordsLinked to original sources
PubMed1990

[Effect of alloxans on pancreatic B-cells with special regard to the alloxan-metal-complex theory. I. Effects of alloxan, alloxan-zinc chelates, dilauric acid and colchicine on blood sugar and rate of mitosis of B-cell Langerhans islets].

Alloxan, alloxan-zinc-chelate, sodium salt of dialuric acid, and colchicine significantly raised the blood sugar level under the previously mentioned experimental conditions 28 h after the application. The typical three-phase blood sugar curve development after alloxan (initial hyperglycemia, hypoglycemia, permanent hyperglycemia) was only approximately reached by dialuric acid which initiated, however, instead of the initial hyperglycemia a more pronounced hypoglycemic phase within the first 6 h. Alloxan-zinc-chelate protractedly and significantly made the blood sugar's increase up to the 7th d post injectionem, without being able to maintain a permanent hyperglycemia with half-normal dosage in comparison with alloxan. Non-diabetogenic alloxan doses (19 mg/kg i. v.) and the appropriate alloxan-zinc-chelate dosage (35 mg/kg) led to a significant increase of the blood sugar only in the chelate group with the long-term test up to 10 d, suggesting an increased and prolonged effect of the metal-chelates by stabilization of alloxan. The tested substances differently acted on the mitotic frequency of B-cells. The mitosis did not increase in the alloxan-zinc- and dialuric acid treated animals and was similar to normal animals far below the fractions of 1/10(6). A 4- and 5-fold increase of the mitotic frequency in the colchicine or alloxan treated animals as well as an accumulation of delayed metaphases suggest an impeded transition to the anaphase and include alloxan among the mitotic poisons.

Alloxan↗
PubMed1990

[Mechanism of action of alloxan on pancreatic B-cells with special regard to the alloxan-metal-complex theory. II. Actions of alloxan, alloxanic acid, Zn2+ and ethyleneglycol-bis-(beta-aminoethylether)-N,N'tetraacetic acid (EGTA) on the assembly of microtubule proteins (MTP) into microtubules or MPT sheets in vitro].

Analyses of the cell structures in the islets of Langerhans revealed the presence of 2 predominant cations, calcium (beta-granules and saccules, mitochondria, sac membranes, and cell membranes) and zinc (secretory granules, encasing membraneous sacs) in association with organelles which involve directional secretion. Both elements are known to interact with microtubules influencing their structural and functional properties, e.g. movement of secretory granules. Influences of Zn2+ on microtubules are investigated with a view to interactions in vitro with and without diabetogenic substances. Turbidimetry and electron microscopic investigations showed that under the conditions mentioned above, alloxan of a concentration of 2 x 10(-5) mol/l (alloxan/tubulin 1:1) inhibits the formation of microtubules and increases the portion of microtubules stabilized of 4 degrees C. The Zn2(+)-induced formation of MTP sheets is not influenced by alloxan and the metal complex forming agent EGTA, if the molar concentrations of the substance and Zn2+ are equally high. With a molar proportion of 2:1 (EGTA:Zn2+), the formation of sheets does not longer occur and only microtubules are formed, whereas neither sheets nor microtubules were assembled by alloxan with this molar proportion. However, neither the assembly of microtubules nor the formation of Zn2(+)-induced sheets are influenced by alloxanic acid in both molar proportions. It is shown that the diabetogenic alloxan influences the formation of microtubules and that performed microtubules are destroyed. This result of alloxan corresponds to its antimitotic activity analogously to the wellknown effect of colchicine (s. Schmidt et al. 1990).(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗
PubMed1975

The mechanism of alloxan toxicity: an indication for alloxan complexes in tissues and alloxan inhibition of 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid (SITS) binding for the liver cell membrane.

It is shown that alloxan inhibits binding of SITS to liver cells. This indicates the cell membrane as a site of alloxan action. Alloxan is found to react with tissues to form complexes that are detectable up to 3 hrs after alloxan treatment. On the basis of the present findings, an assumption is made that alloxan inhibits a cell membrane processes by blockade of functionally importnat groups.

Alloxan↗
PubMed1989

Alloxan-induced alterations in composition and dynamics of red blood cell membranes. I. Effect of alloxan on intact red blood cells and isolated erythrocyte membranes.

Changes of dynamics and chemical composition in membranes of intact red blood cells and isolated erythrocyte membranes treated with alloxan were investigated in order to assess whether alloxan-induced generation of active forms of oxygen may be critical for erythrocyte destroying. In vitro incubation of native red blood cells or prepared erythrocyte membrane ghosts with various concentrations of alloxan gave rise both to levels of membrane TBA-reacting substance and lipid membrane microviscosity both in the deeper and surface regions of lipid bilayer, as evidenced by fluorescence polarization technique. The amount of membrane phospholipid decreased upon alloxan action and that of membrane cholesterol remained rather unchangeable, thus resulting in significant elevation of membrane cholesterol:phospholipid (C:PL) ratio. Both time course and concentration effect of alloxan were found to change exponentially with the different rates of the reaction. There was a linear correlation between 1,6-diphenylhexatriene-1,3,5 (DPH) and 1-anilinonaphthalene-8-sulfonate (ANS) anisotropy coefficients and C:PL ratio (respectively r = 0.697 and r = 0.580) as well as TBARS levels (r = 0.386 for rDPH and r = 0.324 for rANS), thus implying the possible effect of membrane dialdehydes on bilayer components immobilization. Regression coefficients significance testing showed reaction rates of TBARS and C:PL changes to be significantly parallel, contrary to those of fluorescence anisotropy coefficients assessing considerably slower dynamics of alloxan-induced changes. The relevance of changes induced by alloxan in isolated erythrocyte ghosts and intact red blood cells and the compatibility of the present results with several previous studies support the widespreading idea pointing the cell membrane as a main target of damage during alloxan action.

Adult↗
PubMed1989

Generation of alloxan free radicals in chemical and biological systems: implication in the diabetogenic action of alloxan.

Electron spin resonance (ESR) studies that on reaction with NADPH, alloxan was reduced forming labile anion radicals giving a 7-line signal with g = 2.005. These radicals were also produced on incubation of alloxan with rat liver subcellular fractions and their production was greatly enhanced by NADPH. Alloxan effectively scavenged superoxide anion generated by a xanthine-xanthine oxidase (XOD) system in association with its reduction to these anion radicals. These radicals were also formed during incubation of alloxan with rat pancreatic beta-cells. These results suggest that the cytotoxicity of alloxan is related to the formation of alloxan anion radicals.

Alloxan↗
PubMed1989

Generation of free radicals by alloxan in the presence of bovine serum albumin: a role of protein sulfhydryl groups in alloxan cytotoxicity.

The interaction of alloxan with bovine serum albumin was studied. When alloxan was incubated with bovine serum albumin, oxygen consumption, H2O2 formation, and diminution of sulfhydryl groups of the protein were observed. During the reaction of alloxan with the protein, superoxide radicals were generated; and under anaerobic conditions, ESR signal of alloxan free radicals was observed. These results strongly suggest that alloxan mediates electron transfer from the protein sulfhydryl groups to oxygen.

Alloxan↗
PubMed1977

The endocrine pancreas in early alloxan diabetes. Including study of the alloxan inhibitory effect of feeding and some hexoses.

Starved animals were sensitive to alloxan, whereas a more or less inhibitory effect towards alloxan was observed in fed animals, and in starved animals pretreated with glucose, mannose or fructose, but not in those pretreated with galactose. The islets of starved controls possessed larger B-cell mitochondria than those of fed ones. The earliest B-cell changes in the alloxan-treated animals were localized to the mitochondria which showed swelling, and disruption of inner and occasionally outer membranes. Later, many mitochondria were disintegrated, and the endoplasmic reticulum and Golgi complex disorganized. The secretory granules were preserved, although sometimes with atypical configuration, in degenerating but non-necrotic B-cells, suggesting that insulin stored in granules is not released until the cells are necrotic. Finally, frank necrosis was seen in some B-cells, whereas others were unaffected. The Ca2+-precipitation studied by pyroantimonate technique and x-ray analysis differed in the B-cells of the alloxan-treated animals from that in the controls; the former animals exhibited no or only sparse precipitation in mitochondria and secretory granules, but a rich precipitation in the cytoplasmic ground substance, whereas the precipitation in the controls mainly was localized to mitochondria and secretory granules. The primary site of alloxan action in the B-cells is believed to be localized to the mitochondria.

Animals↗
PubMed1983

Loss of a priming effect of glucose on A and D cell secretion in perfused pancreases from alloxan-diabetic rats: role of insulin and alloxan.

Under normal conditions, glucose acutely influences pancreatic islet B, A and D cell secretion. In addition, prior exposure to glucose modulates the secretory responsiveness of these cells (priming effect). We have tested whether alloxan diabetes influences priming effects of glucose on A and D cell secretion. Rat pancreases were perfused 72 h after alloxan treatment. A 20 min infusion of 27.7 mmol/l of glucose failed to induce priming effects, i.e. it did not inhibit the glucagon nor amplify the somatostatin response to a subsequent (15 min later) infusion of 8 mmol/l of arginine. Insulin treatment in vivo for 48 h restored a priming effect of glucose on glucagon secretion in the perfused pancreas, i.e. exposure to 27.7 mmol/l of glucose now inhibited subsequent arginine-induced glucagon secretion by 48% relative to a stimulation period with arginine preceding the glucose pulse (from 5.0 +/- 0.7 to 2.6 +/- 0.5 ng/min, p less than 0.01). Conversely, insulin treatment in vivo did not restore a priming effect of glucose on somatostatin secretion. Other effects noted were failure of 27.7 mmol/l glucose to stimulate, during its presence, the release of somatostatin from pancreases of the diabetic rats whether untreated or insulin-treated. Furthermore, insulin treatment abolished the arginine-induced somatostatin secretion observed in pancreases from untreated rats. It is concluded that short-term alloxan diabetes leads to loss of a priming effect of glucose on glucagon secretion and that this abnormality is secondary to direct or indirect effects of insulinopenia. Concomittant abnormalities of glucose regulation of somatostatin secretion may, in part, be secondary to a cytotoxic effect of alloxan on the D cell.

Alloxan↗
PubMed1982

Superoxide dismutase-inhibitible reduction of cytochrome c by the alloxan radical. Implications for alloxan cytotoxicity.

Cytochrome c was reduced when superoxide was generated from xanthine oxidase in the presence of alloxan, and by the reaction of alloxan and with reduced glutathione. In each case, most of the reduction was inhibited by superoxide dismutase, but considerably more enzyme was required than with superoxide alone. This indicates that the superoxide dismutase-inhibitible cytochrome c reduction was mainly due to a direct reaction with the alloxan radical, and implies that other reactions that are inhibited by superoxide dismutase could be due to either alloxan radicals or superoxide.

Alloxan↗