Changes in serum corticosterone levels and adrenal cortex nitric oxide synthase activity in streptozotocin-diabetic rats: involvement of oxidative stress

REPETTO E.M.; CIPELLI J.M.; SÁNCHEZ R.; ASTORT F.; MARTINEZ CALEJMAN C; DI GRUCCIO J.M.; PIROLI G.G.; ARIAS P.; CYMERYNG C. B.

Roma (Italia)

Congreso; 44th Meeting of the European Association for the Study of Diabetes (EASD); 2008

European Association for the Study of Diabetes (EASD)

Background and aims: Increased oxidative stress, arising as a consequence of excess fuel supply, has been associated with the pathogenesis of chronic diabetic complications. The aim of the present study was to evaluate different parameters of oxidative stress and its role in the induction of nitric oxide synthase (NOS) activity in the adrenal cortex of streptozotocin (STZ)-diabetic rats. The impact of STZ-induced diabetes and of antioxidant treatment on corticosterone secretion was also evaluated. Materials and methods: Male Wistar rats were treated with STZ (40 mg/kg i.p. for three consecutive days) or citrate buffer (controls). After instauration of hyperglycemia, different groups of STZ-treated and control animals received antioxidant treatment (melatonin 7.5 mg/kg p.o. or a-tocopherol 100 mg/kg, p.o.). Thiobarbituric acid-reactive substances (TBARS, an index of lipid peroxidation), HO-1  xpression, superoxide dismutase (SOD), catalase and NOS activities, and reduced glutathione (GSH) levels were determined in adrenal cortex homogenates at different time points after the induction of the diabetic state. Serum corticosterone levels were measured by RIA. Statistic evaluation was performed using an ANOVA followed by Tukey´s post hoc test. Results: after 4 weeks of treatment STZ-diabetic animals showed a significant increase in basal corticosterone levels (101 ± 8.7 versus 49.7 ± 2.0 ng/ml; mean ± SEM) and in tissue TBARS concentrations,as compared to controls. NOS activity was increased from the second to the eighth week of treatment. GSH and antioxidant enzyme activities (HO-1, SOD and catalase) were increased by 4-8 weeks. Antioxidant treatment reduced TBARS levels and prevented the increase in HO-1 and NOS activity. Corticosterone levels were clearly reduced in melatonin and a-tocopherol-treated diabetic animals (43.4 ± 6.1 and 45.6 ± 10.4 ng/ml, respectively). Conclusion: Our results suggest that, in the adrenal cortex of STZ-treated rats, increased oxidative stress is associated with an increase in NOS activity. Upregulation of HO-1, SOD and catalase activities is probably involved in cytoprotective mechanisms triggered by the production of reactive oxygen or nitrogen species, or by other parameters of cell damage associated with the diabetic state. As described previously, STZ-induced diabetes resulted in elevated corticosterone levels; this increase was not present in diabetic animals receiving antioxidant treatment. Accordingly, the involvement of oxidative stress-induced mechanisms in the dysregulation of the hypothalamic-pituitary-adrenal axis observed in STZ-treated animals is postulated.