دورية أكاديمية
Impaired HPA axis function in diabetes involves adrenal apoptosis and phagocytosis.
العنوان: | Impaired HPA axis function in diabetes involves adrenal apoptosis and phagocytosis. |
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المؤلفون: | Repetto EM; Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. erepetto@fmed.uba.ar.; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina. erepetto@fmed.uba.ar., Wiszniewski M; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina., Bonelli AL; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina., Vecino CV; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina., Martinez Calejman C; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina., Arias P; Departamento de Fisiología, Facultad de Medicina, Universidad Nacional de Rosario, Rosario, Argentina., Cymeryng CB; Facultad de Medicina, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Laboratorio de Endocrinología Molecular (LEM), Universidad de Buenos Aires, Buenos Aires, Argentina.; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. |
المصدر: | Endocrine [Endocrine] 2019 Mar; Vol. 63 (3), pp. 602-614. Date of Electronic Publication: 2018 Sep 21. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Humana Press Country of Publication: United States NLM ID: 9434444 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0100 (Electronic) Linking ISSN: 1355008X NLM ISO Abbreviation: Endocrine Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Feb. 1996- : Totowa, NJ : Humana Press Original Publication: Houndsmills, Basingstoke, Hants, UK : Macmillan Press, c1994- |
مواضيع طبية MeSH: | Oxidative Stress*, Adrenal Cortex/*metabolism , Diabetes Mellitus, Experimental/*metabolism, Animals ; Apoptosis ; Corticosterone/blood ; Hypothalamo-Hypophyseal System/metabolism ; Macrophage Activation ; Male ; Pituitary-Adrenal System/metabolism ; Rats, Wistar |
مستخلص: | Purpose: The aim of the present study was to analyze the involvement of oxidative stress and inflammation in the modulation of glucocorticoid 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 and antioxidant enzymes were determined in adrenocortical tissues. Apoptosis and macrophage activation were evaluated by immunohistochemistry (TUNEL and ED1 + ). Basal and ACTH-stimulated corticosterone production were assessed by RIA and plasma ACTH levels were determined by an immunometric assay. Results: Diabetic rats showed a diminished response to exogenous ACTH stimulation along with higher basal corticosterone and lower plasma ACTH levels. In the adrenal cortex we determined an increase in the levels of lipoperoxides, S-nitrosothiols, nitric oxide synthase activity and nitro-tyrosine modified proteins while catalase activity and heme oxygenase-1 expression levels were also elevated. Antioxidant treatments were effective in the prevention of these effects, and in the increase in the number of apoptotic and phagocytic (ED1 + ) cells detected in diabetic rats. No changes were observed in the STZ + INS group. Conclusions: Generation of oxidative/nitrosative stress in the adrenal cortex of diabetic rats leads to the induction of apoptosis and the activation of adrenocortical macrophages and is associated with an elevated basal corticosteronemia and the loss of the functional capacity of the gland. |
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معلومات مُعتمدة: | PICT 2008 N°1034 International Agencia Nacional de Promoción Científica y Tecnológica; UBACYT 2014-2017 20020130100115BA International Universidad de Buenos Aires; UBACYT 2016-2018 20020150200065BA International Universidad de Buenos Aires; PIP11220120100257 International Consejo Nacional de Investigaciones Científicas y Técnicas |
فهرسة مساهمة: | Keywords: Apoptosis; Diabetes; HPA dysfuntion; Oxidative stress; α-lipoic acid; α-tocopherol |
المشرفين على المادة: | W980KJ009P (Corticosterone) |
تواريخ الأحداث: | Date Created: 20180923 Date Completed: 20200427 Latest Revision: 20210213 |
رمز التحديث: | 20240628 |
DOI: | 10.1007/s12020-018-1755-5 |
PMID: | 30242601 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1559-0100 |
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DOI: | 10.1007/s12020-018-1755-5 |