Abstract
A decrease in superoxide dismutase (SOD), the first cellular defence against free radicals, occurs at about the same time as the activation of macrophages within the islets of low-dose streptozocin (LDS)-treated mice. Furthermore, a decrease in the total islet capillary area also has been shown to occur by 10 days after the first streptozocin (STZ) injection and this decline in capillary area is concomitant with the activation of macrophages as is the fall in SOD. Intracellular levels of SOD have been shown to increase after administration of acetyl-homocysteine-thiolactone (citiolone); therefore, the aim of the present study was to observe any relationship between the citiolone-induced increase in SOD levels and islet microvasculature area during LDS-induced diabetes. C57BL6/J male mice were pretreated with daily intramuscular injections of 50 mg citiolone/kg body wt. for 30 days and were then rendered diabetic with 45 mg STZ/kg body wt. given for 5 days; citiolone was given until the animals were killed (days 6, 11 and 18 after the first STZ injection). Further animals were used as non-diabetic and diabetic (STZ-only) controls. The results show that LDS-treated animals when given citiolone: (1) were generally normoglycaemic; (2) had SOD levels that were higher than those of STZ-only control animals; (3) had an islet capillary area that was larger than that of LDS-treated mice. Therefore, the administration of a free radical scavenger, namely citiolone, is able partly to counteract and delay the reduction of islet vascular area and oedema formation in LDS-treated mice.
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Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624
Charlton BA, Bacelj A, Mandel TE (1988) Administration of silica particles or anti-Lyt2 antibody prevents B-cell destruction in NOD mice given cyclophosphamide. Diabetes 37:930–935
Eizirik D (1988) Interleukin-1 induced impairment in pancreatic islet oxidative metabolism of glucose is potentiated by tumor necrosis factor. Acta Endocrinol (Copenh) 119:321–325
Gomori GE (1941) The distribution of phosphatase in normal organs and tissues. J Cell Comp Physiol 17:71–84
Grankvist K, Marklund SL, Taljedal IB (1981) Cu-Zn superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 199:393–398
Kolb-Bachofen V, Epstein S, Kiesel U, Kolb H (1988) Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single cell insulitis before diabetes onset. Diabetes 37:21–27
Krönke KD, Suschek A, Kolb-Bachofen V (1993) Cultured rat islet endothelial cells: nitric oxide production depends on glucose concentration. Diabetes 42 (suppl 1) 148A
Like AA, Rossini AA (1976) Streptozocin-induced pancreatic insulitis: a new model of diabetes mellitus. Science 193:415–417
Like AA, Biron CA, Weringer EJ, Byman K, Stroczynski E, Guberski DL (1986) Prevention of diabetes in Bio Breeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. J Exp Med 164:1145–1159
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Marklund S and Marklund G (1974) Involvement of the superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Mendola J, Wright JR, Lacy PE (1989) Oxygen free radical scavengers and immune destruction of murine islets in allograft rejection and multiple low-dose streptozocin-induced insulitis. Diabetes 38:379–385
Nomikos IN, Wang Y, Lafferty KJ (1989) Involvement of O2 radicals in autoimmune diabetes. Immunol Cell Biol 67:85–87
Papaccio G (1991) Prevention of low-dose streptozocin-induced diabetes by acetyl-homocysteine-thiolactone. Diabetes Res 13:95–102
Papaccio G, Chieffi Baccari G (1992) Alterations of islet microvasculature in mice treated with low dose streptozocin. Histochemistry 97:371–374
Papaccio G, Esposito V (1992) Ultrastructural observations on cytotoxic effector cells infiltrating pancreatic islets of low-dose streptozocin-treated mice. Virchows Arch [A] 420:5–10
Papaccio G, Pisanti FA, Frascatore S (1986) Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin. Diabetes 35:470–474
Papaccio G, Chieffi Baccari G, Mezzogiorno V, Esposito V (1990) Capillary area in early low-dose streptozocin-treated mice. Histochemistry 95:19–21
Papaccio G, Linn T, Federlin K, Volkman A, Esposito V, Mezzogiorno V (1991a) Further morphological and biochemical observations on early low dose streptozocin diabetes in mice. Pancreas 6:659–667
Papaccio G, Frascatore S, Esposito V, Pisanti FA (1991b) Early macrophage infiltration in mice treated with low dose streptozocin decreases islet superoxide dismutase levels. Prevention by silica pre-treatment. Acta Anat 142:141–146
Pisanti FA, Frascatore S, Papaccio G (1988) Superoxide dismutase activity in the BB rat: a dynamic time-course study. Life Sci 43:1625–1632
Rabinovitch A, Suarez WL, Thomas PD, Strynadka K, Simpson I (1992) Cytotoxic effects of cytokines on rat islets: evidence for involvement of free radicals and lipid peroxidation. Diabetologia 35:409–413
Sumoski W, Baquerizo H, Rabinovitch A (1989) Oxygen free radical scavengers protect rat islet cells from damage by cytokines. Diabetologia 32:792–796
Svensson AM, Jansson L, Hellerström C (1988) The volume and area of the capillaries in the endocrine and exocrine pancreas of the rat. Histochemistry 90:43–47
Weibel ER (1979) Stereological methods, vol I. Academic Press, London
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Papaccio, G., Frascatore, S. & Pisanti, F.A. An increase in superoxide dismutase counteracts islet vascular alterations in low-dose streptozocin-treated mice. Histochemistry 101, 215–221 (1994). https://doi.org/10.1007/BF00269547
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DOI: https://doi.org/10.1007/BF00269547