Antioxidant treatment normalizes adrenocortical nitric oxide synthase activity and steroid secretion in streptozotocin-diabetic Wistar rats

SANCHEZ R; REPETTO EM; CIPELLI J; GIORDANINO E; ASTORT F; MARTINEZ CALEJMAN C; MERCAU M; ARIAS P; CYMERYNG C

San Diego, California, EEUU

Congreso; The Endocrine Society’s 92nd Annual Meeting; 2010

Endocrine Society

We previously demonstrated that streptozotocin-induced (STZ) diabetes enhances adrenocortical oxidative / nitrosative stress, modulating basal and ACTH dependent steroid production. Consequently, present studies were designed to evaluate the effect of antioxidant treatment on oxidative stress parameters, nitric oxide synthase (NOS) activity, and steroidogenic function in the adrenal cortex of STZ-diabetic rats.Control (CON) and STZ-treated male Wistar rats (40 mg/kg ip for two consecutive days) received -tocopherol (-T, 200 mg/kg po), tioctic acid (TA, 90 mg/kg ip), or the corresponding vehicle every 48 hours, beginning simultaneously with the detection of hyperglycemia. After 4 weeks, animals were sacrificed and adrenocortical oxidative stress parameters and NOS activity were measured. In a second series of experiments, basal and ACTH-stimulated corticosterone secretion was determined.Antioxidant treatment with -T or TA had no effect on glycemic levels or on body or relative adrenal weight. On the other side, these treatments abolished the increase in TBARS and carbonyl content, and in the expression levels of catalase and heme oxygenase-1 detected in adrenal cortex homogenates of STZ-treated rats. Both antioxidants prevented the increase in NOS activity (CON 88.50.5, STZ 216.79.2, STZ+ -T 108.67.4, STZ+TA 117.416.8 pmol/min/mg protein; p<0.01 vs STZ), and normalized basal (CON 7.32.5, STZ 71.79.2, STZ+ -T 5.83.4, STZ+TA 19.15.5 ng/ml; p<0.001 vs STZ) and ACTH-stimulated corticosterone output in diabetic rats. Neither antioxidant treatment modified NOS activity or corticosterone secretion in CON animals.Our results show that, in STZ-diabetic rats, enhanced oxidative stress is associated with an increase in the activity of the NO-generating system, a well-known local modulator of steroid production in the adrenal cortex, and with altered corticosterone secretion. Systemic antioxidant treatment not only normalized adrenocortical oxidative stress parameters and NOS activity in STZ-treated rats, but also corrected the dysregulation in steroid secretion present in these animals.Sources of Research Support: ANPCyT PICT 2005 N 38283, UBACYT M014 2008-2010; CONICET PIP5