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Start Over Author "Howarth, G.S." Publisher elsevier bv
19 results on '"Howarth, G.S."'

19. Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats

Author

Mark S. Geier, Ross N. Butler, Gordon S. Howarth, Jodie L. Dyer, Johanna C. Cool, Cory J. Xian, Butler, Ross Norman, Xian, Cory Jianke, Cool, J, Dyer, J, Geier, Martin, and Howarth, G.S.

Subjects
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
Abstract

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.

Published
2005

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