Gender-differences of in vitro colonic motility after chemo- and radiotherapy in humans

BMC Pharmacol Toxicol. 2018 Aug 3;19(1):49. doi: 10.1186/s40360-018-0238-x.

Abstract

Background: The aim of the present in vitro study was to investigate, in different genders, motor responses in surgical colonic specimens from patients with rectal cancer undergoing and not undergoing chemotherapy with capecitabine and radiotherapy.

Methods: This in vitro study was conducted from October 2015 to August 2017 at the Experimental Pharmacology Laboratory at the National Institute "S. de Bellis" after collecting samples at the Department of Surgery. Segments of sigmoid colon were obtained from 15 patients (Male (M)/Female (F) = 8/7; control group, CG) operated on for elective colorectal resection for rectal cancer without obstruction and 14 patients (M/F = 7/7; study group, SG) operated on for elective colorectal resection for rectal cancer who also received chemotherapy, based on capecitabine twice daily, and radiotherapy. Isometric tension was measured on colonic circular muscle strips exposed to increasing carbachol or histamine concentrations to obtain concentration-response curves. The motor responses to electrically evoked stimulation were also investigated.

Results: In males, carbachol and histamine caused concentration-dependent contractions in the CG and SG. An increased sensitivity and a higher response to carbachol and histamine were observed in SG than CG (P < 0.01). On the contrary, in females, the response to carbachol was not significantly different in CG from the SG and the maximal responses to carbachol were greater in CG than in SG (P < 0.001). The same applied to histamine for half-maximal effective concentrations and maximal response in that they were not significantly different in CG from the SG. Electrically evoked contractions were significantly more pronounced in males, especially in the SG (P < 0.05).

Conclusions: This preliminary in vitro study has shown gender differences in motor responses of colonic circular muscle strips in patients who had received chemotherapy with capecitabine and radiotherapy.

Keywords: Capecitabine; Carbachol; Chemotherapy; Gender; Histamine; Human colon; Motility; Nitrergic pathways; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Capecitabine / therapeutic use*
  • Colon / physiology*
  • Electric Stimulation
  • Female
  • Gastrointestinal Motility / drug effects*
  • Humans
  • In Vitro Techniques
  • Male
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / radiotherapy*
  • Sex Characteristics*

Substances

  • Antineoplastic Agents
  • Capecitabine