Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin

Mohamed A. Fahim, Hazem Kataya, Rkia El-Kharrag, Dena Am Amer, Basel Al-Ramadi, Sherif M. Karam

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

AIM: To examine the influence of ghrelin on the regenerative potential of gastrointestinal (GI) epithelium. METHODS: Damage to GI epithelium was induced in mice by two intravenous injections of doxorubicin (10 and 6 mg/kg). Some of the doxorubicin-treated mice received a continuous subcutaneous infusion of ghrelin (1.25 μg/h) for 10 d via implanted mini-osmotic pumps. To label dividing stem cells in the S-phase of the cell cycle, all mice received a single intraperitoneal injection of 5'-bromo-2'-deoxyuridine (BrdU) one hour before sacrifice. The stomach along with the duodenum were then removed and processed for histological examination and immunohistochemistry using anti-BrdU antibody. RESULTS: The results showed dramatic damage to the GI epithelium 3 d after administration of chemotherapy which began to recover by day 10. In ghrelin-treated mice, attenuation of GI mucosal damage was evident in the tissues examined post-chemotherapy. Immunohistochemical analysis showed an increase in the number of BrdU-labeled cells and an alteration in their distribution along the epithelial lining in response to damage by doxorubicin. In mice treated with both doxorubicin and ghrelin, the number of BrdU-labeled cells was reduced when compared with mice treated with doxorubicin alone. CONCLUSION: The present study suggests that ghre-lin enhances the regenerative potential of the GI epithelium in doxorubicin-treated mice, at least in part, by modulating cell proliferation.

Original languageEnglish
Pages (from-to)3836-3841
Number of pages6
JournalWorld Journal of Gastroenterology
Volume17
Issue number33
DOIs
Publication statusPublished - Sep 7 2011

Keywords

  • Gastrointestinal cell proliferation
  • Gastrointestinal mucosal damage
  • Ghrelin

ASJC Scopus subject areas

  • Gastroenterology

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