Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats
| Autor: | Mark S. Geier, Ross N. Butler, Gordon S. Howarth, Jodie L. Dyer, Johanna C. Cool, Cory J. Xian |
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| Přispěvatelé: | Butler, Ross Norman, Xian, Cory Jianke, Cool, J, Dyer, J, Geier, Martin, Howarth, G.S. |
| Rok vydání: | 2005 |
| Předmět: |
Male
Antimetabolites Antineoplastic Sucrose medicine.medical_specialty Time Factors Duodenum Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Intraperitoneal injection Crypt Apoptosis Ileum Medical Biochemistry and Metabolomics digestive system Gastroenterology Rats Sprague-Dawley Jejunum Insulin-like growth factor Endocrinology Internal medicine Intestine Small medicine Mucositis Animals Insulin-Like Growth Factor I Intestinal Mucosa Coloring Agents Cell Proliferation Inflammation Chemotherapy business.industry Body Weight digestive oral and skin physiology Organ Size medicine.disease Rats medicine.anatomical_structure Bromodeoxyuridine Fluorouracil Biochemistry and Cell Biology business Sucrase |
| Zdroj: | Growth Hormone & IGF Research. 15:72-82 |
| ISSN: | 1096-6374 |
| DOI: | 10.1016/j.ghir.2004.12.002 |
| Popis: | Insulin-like growth factor-I (IGF-I) has been demonstrated to enhance mucosal repair following intestinal damage induced by chemotherapeutic agents (intestinal mucositis). However, the potential for prophylactic IGF-I to protect the intestine remains undefined. We investigated the effects of IGF-I pre-treatment on chemotherapy-induced mucositis in rats. Male Sprague Dawley rats were treated for 7 days with 0 or 4.3 mg/kg/day IGF-I delivered systemically via osmotic mini-pump. Rats received an intraperitoneal injection of 0 or 150 mg/kg 5-fluorouracil (5-FU) on day 7 and were killed 48 h later for assessment of intestinal damage and repair. Compared to normal controls, 5-FU decreased epithelial proliferation by 86%, concurrently increasing the incidence of apoptosis 87-fold, whilst decreasing small intestinal (SI) length by 14%, SI weight by 30% and total gut weight by 24%. 5-FU decreased villus height in the duodenum (23%), jejunum (20%) and ileum (30%) with crypt depths decreased by 31%, 27% and 33% in these gut regions. These effects were less profound in IGF-I pre-treated rats in which apoptosis was increased 48-fold, with SI length decreased by 7%, SI weight by 18% and total gut weight by 15% accompanied by decreases in villus height of 8% (duodenum), 14% (jejunum) and 21% (ileum), and crypt depth decreases of 23%, 16% and 17% for the same gut regions, compared to normal controls. We conclude that IGF-I pre-treatment only partially attenuates features of intestinal mucositis when assessed 48 h after 5-FU chemotherapy. |
| Databáze: | OpenAIRE |
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