AN INCREASE IN SUPEROXIDE-DISMUTASE COUNTERACTS ISLET VASCULAR ALTERATIONS IN LOW-DOSE STREPTOZOCIN-TREATED MICE

A decrease in superoxide dismutase (SOD), the first cellular defence a gainst free radicals, occurs at about the same time as the activation of macrophages within the islets of low-dose streptozocin (LDS)-treate d 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-homo cysteine-thiolactone (citiolone); therefore, the aim of the present st udy was to observe any relationship between the citiolone-induced incr ease 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 re ndered 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 di abetic (STZ-only) controls. The results show that LDS-treated animals when given citiolone: (1) were generally normoglycaemic; (2) had SOD l evels 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 ci tiolone, is able partly to counteract and delay the reduction of islet vascular area and oedema formation in LDS-treated mice.