{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:41:44Z","timestamp":1789789304458,"version":"4.0.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[1993,8,1]],"date-time":"1993-08-01T00:00:00Z","timestamp":744163200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[1993,8]]},"DOI":"10.1007\/bf00401140","type":"journal-article","created":{"date-parts":[[2004,11,9]],"date-time":"2004-11-09T06:17:11Z","timestamp":1099981031000},"page":"707-715","source":"Crossref","is-referenced-by-count":17,"title":["Alloxan cytotoxicity is highly potentiated by plasma membrane- and lysosomal-associated iron ? a study on a model system of cultured J-774 cells"],"prefix":"10.1007","volume":"36","author":[{"given":"H.","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U. T.","family":"Brunk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"CR1","first-page":"367","volume-title":"Enzyme and metabolic inhibitors vol. III","author":"JL Webb","year":"1966","unstructured":"Webb JL (1966) Alloxan. In: Webb JL (ed) Enzyme and metabolic inhibitors vol. III. Academic Press, New York, pp 367?419"},{"key":"CR2","first-page":"485","volume":"22","author":"CC Rerup","year":"1970","unstructured":"Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22: 485?518","journal-title":"Pharmacol Rev"},{"key":"CR3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2337\/diab.16.4.242","volume":"16","author":"KF Wellmann","year":"1967","unstructured":"Wellmann KF, Volk BW, Lazarus SS (1967) Ultrastructural pancreatic beta-cell changes in rabbits after small and large doses of alloxan. Diabetes 16: 242?251","journal-title":"Diabetes"},{"key":"CR4","first-page":"501","volume":"190","author":"RE Heikkila","year":"1974","unstructured":"Heikkila RE, Barden H, Cohen G (1974) Prevention of alloxaninduced diabetes by ethanol administration. J Pharmacol Exp Ther 190: 501?506","journal-title":"J Pharmacol Exp Ther"},{"key":"CR5","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/0006-2952(76)90502-5","volume":"25","author":"RE Heikkila","year":"1976","unstructured":"Heikkila RE, Winston B, Cohen G, Barden H (1976) Alloxan-induced diabetes ? evidence for hydroxyl radical as a cytotoxic intermediate. Biochem Pharmacol 25: 1085?1092","journal-title":"Biochem Pharmacol"},{"key":"CR6","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/BF01949404","volume":"38","author":"RE Heikkila","year":"1982","unstructured":"Heikkila RE, Felicitas SC (1982) The prevention of alloxan-induced diabetes in mice by the iron-chelator detapac: suggestion of a role for iron in the cytotoxic process. Experientia 38: 378?379","journal-title":"Experientia"},{"key":"CR7","doi-asserted-by":"crossref","first-page":"12134","DOI":"10.1016\/S0021-9258(18)43243-7","volume":"256","author":"F Ishibashi","year":"1981","unstructured":"Ishibashi F, Howard BV (1981) Alloxan and H2O2 action on glucose metabolism in cultured fibroblasts. Generation of oxygencontaining free radicals as a mechanism of alloxan action. J Biol Chem 256: 12134?12139","journal-title":"J Biol Chem"},{"key":"CR8","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1016\/0006-2952(82)90285-4","volume":"31","author":"AW Harman","year":"1982","unstructured":"Harman AW, Fischer LJ (1982) Alloxan toxicity in isolated rat hepatocytes and protection by sugars. Biochem Pharmacol 31: 3731?3736","journal-title":"Biochem Pharmacol"},{"key":"CR9","first-page":"555","volume":"19","author":"S Sagstr\u00f6m","year":"1987","unstructured":"Sagstr\u00f6m S, Scarlett SM, Sagulin G-B, Roomans GM (1987) Early effects of alloxan on rat submandibular gland. J Submicrosc Cytol 19: 555?559","journal-title":"J Submicrosc Cytol"},{"key":"CR10","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/0006-2952(89)90414-0","volume":"38","author":"C Watala","year":"1989","unstructured":"Watala C, Budziejewska A, Jozwiak Z (1989) 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. Biochem Pharmacol 38: 1793?1798","journal-title":"Biochem Pharmacol"},{"key":"CR11","doi-asserted-by":"crossref","unstructured":"Kawada T, Arakawa M, Kambara K et al. (1990) Oxygen radicals participate in alloxan-induced pulmonary edema. Proc XII Int Congr Electr Micr, Seattle, pp 298?299 (Abstract)","DOI":"10.1017\/S0424820100159047"},{"key":"CR12","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/j.1699-0463.1991.tb01297.x","volume":"99","author":"H Zhang","year":"1991","unstructured":"Zhang H, Zdolsek J, Brunk U (1991) Effects of alloxan and reducing agents on macrophages in culture. APMIS 99: 1038?1048","journal-title":"APMIS"},{"key":"CR13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1699-0463.1992.tb00878.x","volume":"100","author":"H Zhang","year":"1992","unstructured":"Zhang H, Gao G, Brunk U (1992) Extracellular reduction of alloxan results in oxygen radical-mediated attack on plasma and lysosomal membranes. APMIS 100: 317?325","journal-title":"APMIS"},{"key":"CR14","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1699-0463.1992.tb00877.x","volume":"100","author":"H Zhang","year":"1992","unstructured":"Zhang H, Zdolsek J, Brunk U (1992) Alloxan cytotoxicity involves lysosomal damage. APMIS 100: 309?316","journal-title":"APMIS"},{"key":"CR15","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.3891\/acta.chem.scand.17-1677","volume":"17","author":"C Lagercrantz","year":"1963","unstructured":"Lagercrantz C, Yhland M (1963) Free radicals in the reaction of alloxan with glutathione and ascorbic acid. Acta Chem Scand 17: 1677?1682","journal-title":"Acta Chem Scand"},{"key":"CR16","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1016\/S0021-9258(19)42751-8","volume":"249","author":"G Cohen","year":"1974","unstructured":"Cohen G, Heikkila RE (1974) The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. J Biol Chem 249: 2447?2452","journal-title":"J Biol Chem"},{"key":"CR17","first-page":"426","volume":"3","author":"DW Deamer","year":"1971","unstructured":"Deamer DW, Heikkila RE, Panganamala RV, Cohen G, Cornwell DG (1971) The alloxan-dialuric acid cycle and the generation of hydrogen peroxide. Physiol Chem Phys 3: 426?430","journal-title":"Physiol Chem Phys"},{"key":"CR18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1042\/bj1820017","volume":"182","author":"K Grankvist","year":"1979","unstructured":"Grankvist K, Marklund S, Sehlin J, T\u00e4ljedal I-B (1979) Superoxide dismutase, catalase and scavengers of hydroxyl radical protect against the toxic action of alloxan on pancreatic islet cells in vitro. Biochem J 182: 17?25","journal-title":"Biochem J"},{"key":"CR19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2337\/diab.29.3.213","volume":"29","author":"LJ Fischer","year":"1980","unstructured":"Fischer LJ, Hamburger SA (1980) Inhibition of alloxan action in isolated pancreatic islets by superoxide dismutase, catalase, and a metal chelator. Diabetes 29: 213?216","journal-title":"Diabetes"},{"key":"CR20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1042\/bj2070609","volume":"207","author":"CC Winterbourn","year":"1982","unstructured":"Winterbourn CC (1982) Superoxide dismutase-inhibitable reduction of cytochrome c by the alloxan radical. Biochem J 207: 609?612","journal-title":"Biochem J"},{"key":"CR21","first-page":"3527","volume":"31","author":"W Malaisse","year":"1982","unstructured":"Malaisse W (1982) Alloxan toxicity to the pancreatic ?-cell. A new hypothesis. Biochem Pharmacol 31: 3527?3534","journal-title":"A new hypothesis. Biochem Pharmacol"},{"key":"CR22","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/BF00291975","volume":"28","author":"LG Thaete","year":"1985","unstructured":"Thaete LG, Crouch RK, Buse MG, Spicer SS (1985) The protective role of copper-zinc superoxide dismutase against alloxan-induced diabetes: morphological aspects. Diabetologia 28: 677?682","journal-title":"Diabetologia"},{"key":"CR23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0020-711X(86)90141-2","volume":"18","author":"K Grankvist","year":"1986","unstructured":"Grankvist K, Marklund SL (1986) Effect of extracellularly generated free radicals on the plasma membrane permeability of isolated pancreatic ?-cells. Int J Biochem 18: 109?113","journal-title":"Int J Biochem"},{"key":"CR24","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0006-2952(89)90206-2","volume":"38","author":"CC Winterbourn","year":"1989","unstructured":"Winterbourn CC, Cowden WB, Sutton HC (1989) Auto-oxidation of dialuric acid, divicine and isouramil. Superoxide dependent and independent mechanisms. Biochem Pharmacol 38: 611?618","journal-title":"Biochem Pharmacol"},{"key":"CR25","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0006-2952(89)90037-3","volume":"38","author":"CC Winterbourn","year":"1989","unstructured":"Winterbourn CC, Munday R (1989) Glutathione-mediated redox cycling of alloxan. Mechanisms of superoxide dismutase inhibition and of metal-catalyzed OH\u00b7 formation. Biochem Pharmacol 38: 271?277","journal-title":"Biochem Pharmacol"},{"key":"CR26","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.2337\/diab.40.9.1141","volume":"40","author":"N Takasu","year":"1991","unstructured":"Takasu N, Komiya I, Asawa T, Nagasawa Y, Yamada T (1991) Streptoxocinand alloxan-induced H2O2 generation and DNA fragmentation in pancreatic islets. H2O2 as mediator for DNA fragmentation. Diabetes 40: 1141?1145","journal-title":"Diabetes"},{"key":"CR27","doi-asserted-by":"crossref","first-page":"10099","DOI":"10.1016\/S0021-9258(17)39218-9","volume":"260","author":"PE Starke","year":"1985","unstructured":"Starke PE, Farber JL (1985) Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron-catalyzed Haber-Weiss reaction. J Biol Chem 260: 10099?10104","journal-title":"J Biol Chem"},{"key":"CR28","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1073\/pnas.79.3.927","volume":"79","author":"WJ Malaisse","year":"1982","unstructured":"Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG (1982) Determinants of the selective toxicity of alloxan to the pancreatic ? cell. Proc Natl Acad Sci USA 79: 927?930","journal-title":"Proc Natl Acad Sci USA"},{"key":"CR29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/bj1990393","volume":"199","author":"K Grankvist","year":"1981","unstructured":"Grankvist K, Marklund SL, T\u00e4ljedal I-B (1981) CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 199: 393?398","journal-title":"Biochem J"},{"key":"CR30","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0003-9861(73)90329-9","volume":"156","author":"DJ Danner","year":"1973","unstructured":"Danner DJ, Brignac PJ, Arceneaux D, Patel V (1973) The oxidation of phenol and its reaction product by horseradish peroxidase and hydrogen peroxide. Arch Biochem Biophys 156: 759?763","journal-title":"Arch Biochem Biophys"},{"key":"CR31","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1042\/bj2570561","volume":"257","author":"GD Buffinton","year":"1989","unstructured":"Buffinton GD, \u00d6llinger K, Brunmark A, Cadenas E (1989) DTdiaphorase-catalysed reduction of 1,4-naphthoquinone derivatives and glutathionyl-quinone conjugates. Biochem J 257: 561?571","journal-title":"Biochem J"},{"key":"CR32","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/00007890-196411000-00001","volume":"2","author":"JR Tennant","year":"1964","unstructured":"Tennant JR (1964) Evaluation of the trypan blue technique for determination of cell viability. Transplantation 2: 685?694","journal-title":"Transplantation"},{"key":"CR33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/BF03349305","volume":"2","author":"K Grankvist","year":"1979","unstructured":"Grankvist K, Lernmark \u00c5, T\u00e4ljedal I-B (1979) Trypan blue as a marker of plasma membrane permeability in alloxan-treated mouse islet cells. J Endocrinol Invest 2: 139?145","journal-title":"J Endocrinol Invest"},{"key":"CR34","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1073\/pnas.55.1.134","volume":"55","author":"B Rotman","year":"1966","unstructured":"Rotman B, Papermaster BW (1966) Membrane properties of living mammalian cells as studied by enzymatic hydrolysis of fluorogenic esters. Proc Natl Acad Sci USA 55: 134?141","journal-title":"Proc Natl Acad Sci USA"},{"key":"CR35","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/cyto.990110205","volume":"11","author":"C Dive","year":"1990","unstructured":"Dive C, Watson JV, Workman P (1990) Multiparametric analysis of cell membrane permeability by two colour flow cytometry with complementary fluorescent probes. Cytometry 11: 244?252","journal-title":"Cytometry"},{"key":"CR36","first-page":"335","volume-title":"The microcomputer in cell and neurobiology research","author":"I Rundquist","year":"1985","unstructured":"Rundquist I, Enerb\u00e4ck L (1985) A simple microcomputer system for microscope fluorometry. In: Mize RR (ed) The microcomputer in cell and neurobiology research. Elsevier, New York, pp 335?353"},{"key":"CR37","first-page":"303","volume":"92","author":"I Rundquist","year":"1984","unstructured":"Rundquist I, Olsson M, Brunk U (1984) Cytofluorometric quantitation of acridine orange uptake by cultured cells. Acta Pathol Microbiol Immunol Scand [A] 92: 303?309","journal-title":"Acta Pathol Microbiol Immunol Scand [A]"},{"key":"CR38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1083\/jcb.18.2.237","volume":"18","author":"E Robbins","year":"1963","unstructured":"Robbins E, Marcus PI (1963) Dynamics of acridine orange-cell interaction. I. Interrelationships of acridine orange particles and cytoplasmic reddening. J Cell Biol 18: 237?250","journal-title":"J Cell Biol"},{"key":"CR39","first-page":"706","volume":"46","author":"F Timm","year":"1958","unstructured":"Timm F (1958) Zur Histochemie der Schwermetalle. Das SulfidSilberverfahren. Deut Z Gerichtl Med 46: 706?711","journal-title":"Deut Z Gerichtl Med"},{"key":"CR40","first-page":"345","volume":"31","author":"U Brunk","year":"1968","unstructured":"Brunk U, Brun A, Sk\u00f6ld G (1968) Histochemical demonstration of heavy metals with the sulphide-silver method. A methodological study. Acta Histochem 31: 345?357","journal-title":"Acta Histochem"},{"key":"CR41","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1177\/18.11.820","volume":"18","author":"A Brun","year":"1970","unstructured":"Brun A, Brunk U (1970) Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. J Histochem Cytochem 18: 820?827","journal-title":"J Histochem Cytochem"},{"key":"CR42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF00496691","volume":"55","author":"G Danscher","year":"1978","unstructured":"Danscher G, Zimmer J (1978) An improved Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues. Histochemistry 55: 27?40","journal-title":"Histochemistry"},{"key":"CR43","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0021-9258(18)89697-1","volume":"260","author":"PE Starke","year":"1985","unstructured":"Starke PE, Farber JL (1985) Endogenous defenses against the cytotoxicity of hydrogen peroxide in cultured rat hepatocytes. J Biol Chem 260: 86?92","journal-title":"J Biol Chem"},{"key":"CR44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj2190001","volume":"18","author":"B Halliwell","year":"1984","unstructured":"Halliwell B, Gutteridge JM (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem 18: 1?14","journal-title":"Biochem"},{"key":"CR45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0098-2997(85)90001-9","volume":"8","author":"B Halliwell","year":"1985","unstructured":"Halliwell B, Gutteridge JM (1985) The importance of free radicals and catalytic metal ions in human disease. Mol Aspects Med 8: 89?193","journal-title":"Mol Aspects Med"},{"key":"CR46","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0003-9861(86)90305-X","volume":"246","author":"B Halliwell","year":"1986","unstructured":"Halliwell B, Gutteridge JM (1986) Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys 246: 501?514","journal-title":"Arch Biochem Biophys"},{"key":"CR47","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0006-291X(85)90916-7","volume":"133","author":"PE Starke","year":"1983","unstructured":"Starke PE, Gilbertson JD, Farber JL (1983) Lysosomal origin of the ferric iron is required for cell killing by hydrogen peroxide. Biochem Biophys Res Commun 133: 371?379","journal-title":"Biochem Biophys Res Commun"},{"key":"CR48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3109\/10715769309147344","volume":"18","author":"JM Zdolsek","year":"1993","unstructured":"Zdolsek JM, Zhang H, Roberg K, Brunk UT (1993) H2O2-mediated damage to lysosomal membranes of J-774 cells. Free Rad Res Commun 18: 71?85","journal-title":"Free Rad Res Commun"},{"key":"CR49","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1751-1097.1990.tb01685.x","volume":"51","author":"JM Zdolsek","year":"1990","unstructured":"Zdolsek JM, Olsson MG, Brunk UT (1990) Photooxidative damage to lysosomes of cultured macrophages by acridine orange. Photochem Photobiol 51: 67?76","journal-title":"Photochem Photobiol"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/BF00401140.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/BF00401140\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/BF00401140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:25:13Z","timestamp":1624839913000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/BF00401140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,8]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1993,8]]}},"alternative-id":["BF00401140"],"URL":"https:\/\/doi.org\/10.1007\/bf00401140","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,8]]}}}