title: Alterations in the small intestinal wall and motor function after repeated cisplatin in rat.
abstract: BACKGROUND
  Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin.
  
  
  METHODS
  Male Wistar rats received saline or cisplatin (2 mg kg-1week-1, for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR.
  
  
  RESULTS
  Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent).
  
  
  CONCLUSIONS
  Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated.
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Uranga
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo de Compuestos químicos y materiales nanoestructurados con aplicaciones Avanzadas (QUINANOAP), Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: García-Martínez
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo de Compuestos químicos y materiales nanoestructurados con aplicaciones Avanzadas (QUINANOAP), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: García-Jiménez
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Vera
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Martín-Fontelles
authors.affiliation: Depto. de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC), Madrid, Spain.|Grupo de Excelencia Investigadora URJC-Banco de Santander-Grupo Multidisciplinar de Investigación y Tratamiento del Dolor (i+DOL), Madrid, Spain.|Unidad Asociada I+D+i al Instituto de Química Médica, IQM (CSIC), Madrid, Spain.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-6726-8795
authors.initials: R
authors.lastname: Abalo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: chemotherapy-induced adverse effects; cisplatin; gastrointestinal motility; gene expression; histopathology