HPA Dysfunction in Streptozotocin- Diabetic Rats: Effect of Lipoic Acid and α-Tocopherol Treatment

REPETTO, ESTEBAN M.; BONELLI, ANA L.; SANCHEZ, ROCÍO; MERCAU, MARÍA E.; ARIAS, PABLO; CYMERYNG, CORA B.

Chicago

Congreso; 16th International Congress of Endocrinology & the Endocrine Society?s 96th Annual Meeting & Expo; 2014

The Endocrine Society

Background and aims: We previously demonstrated that streptozotocin-induced (STZ) diabetes in rats entails an increase in oxidative stress in adrenocortical tissue that was associated with altered corticosterone secretion, already evident 4 weeks after diabetes induction. We also showed that systemic antioxidant treatment normalized this parameter. However, data on ACTH levels and the concomitant adrenocortical response in STZ-treated rats was lacking. In order to test the hypothesis that STZ-induced oxidative stress may affect the secretion of ACTH, we analyzed plasma levels of ACTH and glucocorticoid secretion patterns in STZ treated rats and compared them with those observed in non-diabetic animals, with and without lipoic acid (LA) or alpha-tocopherol (αT) treatment. Materials and methods:Male Wistar rats (220-240g BW) were randomly assigned to the following groups: CON (control), STZ (two injections of 40 mg/kg STZ separated by 48 h), LA (90 mg/kg ip every 48 h), alphaT (200 mg/kg po every 48 h), STZ-LA or STZ-alphaT (where LA or alphaT treatment were initiated immediately after the confirmation of STZ-induced hyperglycemia). After 4 weeks, all animals were sacrificed and plasma ACTH and serum corticosterone levels (basal and ACTH-stimulated) were measured. Lipoperoxides (as TBARS) and the expression levels of CYP11A1 and MC2R, key molecules in the modulation of steroidogenesis, were also evaluated by RT-qPCR in the adrenal cortex. Results: Antioxidant treatment with alphaT or LA had no effect on fasting plasma glucose levels in STZ animals. Neither alphaT nor LA prevented the decrease in ACTH circulating levels determined in STZ-treated rats (CON: 40.9±6.8 p