IMPAIRED HPA AXIS FUNCTION IN DIABETES INVOLVES ADRENAL APOPTOSIS AND PHAGOCYTOSIS

REPETTO, EM; WISZNIEWSKI, M; BONELLI, ANA L.; VECINO, CV; MARTINEZ CALEJMAN, C; ARIAS, P; CYMERYNG, CB

ENDOCRINE

HUMANA PRESS INC

Lugar: Oregon; Año: 2018 vol. 63 p. 602 - 614

0969-711X

Purpose: The aim of the present study was to analyze theinvolvement of oxidative stress and inflammation in the modulation ofglucocorticoid production in the adrenal cortex of diabetic rats.  Methods: Male Wistar rats were treated with or without streptozotocin(STZ, an insulinopenic model of diabetes) and either α-lipoic (90 mg/kg ip.),α-tocopherol (200 mg/kg po.) or with STZ and supplemented with insulin(STZ+INS: 2.5U/day) for 4 weeks. Oxidative/nitrosative stress parameters andantioxidant enzymes were determined in adrenocortical tissues. Apoptosis andmacrophage activation were evaluated by immunohistochemistry (TUNEL and ED1+).Basal and ACTH-stimulated corticosterone production were assessed by RIA andplasma ACTH levels were determined by an immunometric assay. Results: Diabetic rats showed a diminished response toexogenous ACTH stimulation along with higher basal corticosterone and lowerplasma ACTH levels. In the adrenal cortex we determined an increase in thelevels of lipoperoxides, S-nitrosothiols, nitric oxide synthase activity andnitro-tyrosine modified proteins while catalase activity and heme oxygenase-1 expressionlevels were also elevated. Antioxidant treatments were effective in theprevention of these effects, and in the increase in the number of apoptotic andphagocytic (ED1+) cells detected in diabetic rats. No changes wereobserved in the STZ+INS group. Conclusions: Generationof oxidative/nitrosative stress in the adrenal cortex of diabetic rats leads tothe induction of apoptosis and the activation of adrenocortical macrophages andis associated with an elevated basal corticosteronemia and the loss of thefunctional capacity of the gland.