Response Variability to Drug Testing in Two Models of Chemically Induced Colitis
Suau, Roger (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Garcia, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bernal, Carla (National University of San Marcos. Laboratory of Genetic Metabolic Diseases, Faculty of Biosciences)
Llaves, Mariona (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Schiering, Katharina (Hannover Medical School. Institute of Transfusion Medicine and Transplant Engineering)
Jou-Ollé, Eva (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pertegaz, Alex (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Garcia-Jaraquemada, Arce (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Bartolí, Ramon (Hepatology Unit IGTP)
Lorén, Violeta (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Vergara, Patri (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Mañosa i Ciria, Míriam (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Domènech, Eugeni (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Manyé, Josep (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)

Data:	2023
Resum:	The lack of knowledge regarding the pathogenesis of IBD is a challenge for the development of more effective and safer therapies. Although in vivo preclinical approaches are critical for drug testing, none of the existing models accurately reproduce human IBD. Factors that influence the intra-individual response to drugs have barely been described. With this in mind, our aim was to compare the anti-inflammatory efficacy of a new molecule (MTADV) to that of corticosteroids in TNBS and DSS-induced colitis mice of both sexes in order to clarify further the response mechanism involved and the variability between sexes. The drugs were administered preventively and therapeutically, and real-time bioluminescence was performed for the in vivo time-course colitis monitoring. Morphometric data were also collected, and colonic cytokines and acute plasma phase proteins were analyzed by qRT-PCR and ELISA, respectively-bioluminescence images correlated with inflammatory markers. In the TNBS model, dexamethasone worked better in females, while MTADV improved inflammation in males. In DSS-colitis, both therapies worked similarly. Based on the molecular profiles, interaction networks were constructed to pinpoint the drivers of therapeutic response that were highly dependent on the sex. In conclusion, our results suggest the importance of considering sex in IBD preclinical drug screening.
Ajuts:	Instituto de Salud Carlos III PI18/00892
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Inflammatory bowel disease ; Crohn's disease ; Ulcerative colitis ; TNBS-induced colitis ; DSS-induced colitis ; Bioluminescence ; Sex ; Inflammation
Publicat a:	International journal of molecular sciences, Vol. 24 (march 2023) , ISSN 1422-0067

DOI: 10.3390/ijms24076424
PMID: 37047397

21 p, 8.7 MB

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