16α‐Bromoepiandrosterone as a new candidate for experimental diabetes‐tuberculosis comorbidity treatment

dc.creatorLópez Torres, Manuel Othoniel
dc.creatorMarquina Castillo, Brenda
dc.creatorRamos Espinosa, Octavio
dc.creatorMata Espinosa, Dulce
dc.creatorBarrios Payan, Jorge A.
dc.creatorBaay Guzman, Guillermina
dc.creatorHuerta Yepez, Sara
dc.creatorBini, Estela Isabel
dc.creatorTorre Villalvazo, Ivan
dc.creatorTorres, Nimbe
dc.creatorTovar, Armando
dc.creatorChamberlin, William
dc.creatorGe, Yu
dc.creatorCarranza, Maria Andrea
dc.creatorHernández Pando, Rogelio
dc.date2021-04
dc.date.accessioned2023-08-31T00:32:46Z
dc.date.available2023-08-31T00:32:46Z
dc.identifierhttp://hdl.handle.net/11336/182410
dc.identifierLópez Torres, Manuel Othoniel; Marquina Castillo, Brenda; Ramos Espinosa, Octavio; Mata Espinosa, Dulce; Barrios Payan, Jorge A.; et al.; 16α‐Bromoepiandrosterone as a new candidate for experimental diabetes‐tuberculosis comorbidity treatment; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 205; 2; 4-2021; 232-245
dc.identifier0009-9104
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8543544
dc.descriptionTuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1). 11-βHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-β-hydroxysteroid dehydrogenase type 2 (11-βHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-βHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-βHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-βHSD1 expression while increasing 11-βHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.
dc.descriptionFil: López Torres, Manuel Othoniel. Instituto Nacional de la Nutrición Salvador Zubiran; México
dc.descriptionFil: Marquina Castillo, Brenda. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Ramos Espinosa, Octavio. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Mata Espinosa, Dulce. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Barrios Payan, Jorge A.. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Baay Guzman, Guillermina. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Huerta Yepez, Sara. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Bini, Estela Isabel. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Torre Villalvazo, Ivan. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Torres, Nimbe. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Tovar, Armando. Instittuto de Ciencias Médicas y Nutrición; México
dc.descriptionFil: Chamberlin, William. No especifíca;
dc.descriptionFil: Ge, Yu. No especifíca;
dc.descriptionFil: Carranza, Maria Andrea. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones En Medicina Traslacional. - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiologicas "prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones En Medicina Traslacional.; Argentina
dc.descriptionFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Medicas y Nutricion; México
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley Blackwell Publishing, Inc
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/cei.13603
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1111/cei.13603
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject11-ΒHSD1
dc.subjectACTIVE GLUCOCORTICOIDS
dc.subjectBEA
dc.subjectCENTRAL NERVOUS SYSTEM
dc.subjectCOLONY-FORMING UNITS
dc.subjectDIABETES–TUBERCULOSIS CO-MORBIDITY
dc.subjectIMMUNOTHERAPY
dc.subjecthttps://purl.org/becyt/ford/3.3
dc.subjecthttps://purl.org/becyt/ford/3
dc.title16α‐Bromoepiandrosterone as a new candidate for experimental diabetes‐tuberculosis comorbidity treatment
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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