Radiographic and histopathological study of gastrointestinal dysmotility in lipopolysaccharide‐induced sepsis in the rat

Author:

Castro Marta123,Valero Marta Sofía123,López‐Tofiño Yolanda45,López‐Gómez Laura56,Girón Rocío478,Martín‐Fontelles María Isabel489,Uranga José A.56ORCID,Abalo Raquel458910ORCID

Affiliation:

1. Departamento de Farmacología, Fisiología y Medicina Legal y Forense Universidad de Zaragoza Zaragoza Spain

2. Instituto de Investigación Sanitaria de Aragón (IIS Aragón) Zaragoza Spain

3. Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza‐CITA Zaragoza Spain

4. Área de Farmacología y Nutrición, Departamento de Ciencias Básicas de la Salud Universidad Rey Juan Carlos (URJC) Alcorcón Spain

5. High‐Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut‐URJC) Alcorcón Spain

6. Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud Universidad Rey Juan Carlos (URJC) Alcorcón Spain

7. High‐Performance Research Group in Experimental Pharmacology (PHARMAKOM‐URJC) Alcorcón Spain

8. Unidad Asociada I+D+i del Instituto de Química Médica (IQM), Consejo Superior de Investigaciones Científicas (CSIC) Madrid Spain

9. Grupo de Trabajo de Ciencias Básicas en Dolor y Analgesia de la Sociedad Española del Dolor Madrid Spain

10. Grupo de Trabajo de Cannabinoides de la Sociedad Española del Dolor Madrid Spain

Abstract

AbstractBackgroundSepsis is a highly incident condition in which a cascade of proinflammatory cytokines is involved. One of its most frequent consequences is ileus, which can increase mortality. Animal models such as that induced by systemic administration of lipopolysaccharide (LPS) are useful to deeply evaluate this condition. The effects of sepsis on the gastrointestinal (GI) tract have been explored but, to our knowledge, in vivo studies showing the motor and histopathological consequences of endotoxemia in an integrated way are lacking. Our aim was to study in rats the effects of sepsis on GI motility, using radiographic methods, and to assess histological damage in several organs.MethodsMale rats were intraperitoneally injected with saline or E. coli LPS at 0.1, 1, or 5 mg kg−1. Barium sulfate was intragastrically administered, and X‐rays were performed 0–24 h afterwards. Several organs were collected for organography, histopathology, and immunohistochemistry studies.Key ResultsAll LPS doses caused gastroparesia, whereas changes in intestinal motility were dose‐and time‐dependent, with an initial phase of hypermotility followed by paralytic ileus. Lung, liver, stomach, ileum, and colon (but not spleen or kidneys) were damaged, and density of neutrophils and activated M2 macrophages and expression of cyclooxygenase 2 were increased in the colon 24 h after LPS 5 mg kg−1.Conclusions and InferencesUsing radiographic, noninvasive methods for the first time, we show that systemic LPS causes dose‐, time‐, and organ‐dependent GI motor effects. Sepsis‐induced GI dysmotility is a complex condition whose management needs to take its time‐dependent changes into account.

Funder

Comunidad de Madrid

Gobierno de Aragón

Ministerio de Ciencia e Innovación

Ministerio de Ciencia, Innovación y Universidades

Publisher

Wiley

Subject

Gastroenterology,Endocrine and Autonomic Systems,Physiology

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