loading page

16a-Bromoepiandrosterone as a new candidate for diabetes-tuberculosis comorbidity treatment
  • +13
  • Manuel Othoniel Lopez Torres,
  • Brenda Marquina,
  • Octavio Ramos-Espinosa,
  • Dulce Mata,
  • Jorge Barrios-Payan,
  • Guillermina Baay,
  • Sara Huerta-Yépez,
  • Cristian Alfredo Segura-Cerda,
  • Estela Bini,
  • Ivan Torre-Villalvazo,
  • Nimbe Torres,
  • Armando R Tovar,
  • William Chamberlin,
  • Yu Ge,
  • Andrea Carranza,
  • Rogelio Hernandez Pando
Manuel Othoniel Lopez Torres
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Author Profile
Brenda Marquina
National Institute of Medical Sciences and Nutrition
Author Profile
Octavio Ramos-Espinosa
National Institute of Medical Sciences and Nutrition Salvador Zubirán
Author Profile
Dulce Mata
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Author Profile
Jorge Barrios-Payan
National Institute of Medical Sciences and Nutrition “Salvador Zubiran”
Author Profile
Guillermina Baay
Oncological Diseases Research Unit, Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico.
Author Profile
Sara Huerta-Yépez
Hospital Infantil de Mexico "Federico Gomez"
Author Profile
Cristian Alfredo Segura-Cerda
Centro de Investigacion y Asistencia en Tecnologia y Diseno del Estado de Jalisco
Author Profile
Estela Bini
National Institute of Medical Sciences and Nutrition ‘‘Salvador Zubirán’’
Author Profile
Ivan Torre-Villalvazo
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Author Profile
Nimbe Torres
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Author Profile
Armando R Tovar
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Author Profile
William Chamberlin
Protibea Therapeutics
Author Profile
Yu Ge
Protibea Therapeutics
Author Profile
Andrea Carranza
Universidad de Buenos Aires
Author Profile
Rogelio Hernandez Pando
National Institute of Medical Sciences and Nutrition
Author Profile

Abstract

Being the leading cause of mortality by a single infectious agent, tuberculosis (TB) continues as one of the most relevant issues of public health. Another pandemic disease is type 2 diabetes mellitus (T2D) is usually associated with immunodeficiency. Thus, an increased prevalence of TB-T2D comorbidity represents one of the most significant challenges for health providers. During the chronic phase of both diseases, several immunoendocrine abnormalities are occurring, but extra-adrenal production of active glucocorticoids (GCs) is a possible deleterious factor in both entities. Active GCs have been related to insulin resistance and suppression of Th1 responses, contributing to T2D and TB pathogenesis. 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1) catalyzes the conversion of inactive GGs in their active form (cortisol or corticosterone in rodents) in the lungs and liver and could be responsible for this immunoendocrine disfunction. Dehydroepiandrosterone (DHEA) is an anabolic adrenal hormone with antagonist effects against GCs on immune cells and glucose metabolism. A synthetic analog of DHEA, the 16a-bromoepindrosterone (BEA), lacks an anabolic effect while keeping his immune and metabolic effect. The therapeutic efficiency of BEA was studied in a murine model of T2D-TB comorbidity. TB-T2D mice underwent more severe lung disease than in TB-infected but non-diabetic animals. BEA decreased the active form of GCs and 11-βHSD1 expression, while increasing 11-βHSD2 expression, which reduced hyperglycemia and liver steatosis, lung bacillary loads, and pneumonia. Thus, it seems that BEA is an efficient therapy to control metabolic and immune abnormalities caused by high active GCs production.

Peer review status:ACCEPTED

09 Sep 2020Submitted to Clinical & Experimental Immunology
27 Oct 2020Submission Checks Completed
27 Oct 2020Assigned to Editor
30 Oct 2020Reviewer(s) Assigned
04 Jan 2021Review(s) Completed, Editorial Evaluation Pending
07 Jan 2021Editorial Decision: Revise Major
05 Mar 20211st Revision Received
15 Mar 2021Reviewer(s) Assigned
22 Mar 2021Review(s) Completed, Editorial Evaluation Pending
23 Mar 2021Editorial Decision: Accept