Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2010

01-04-2010 | Original Article

Optimization of the non-invasive 13C-sucrose breath test in a rat model of methotrexate-induced mucositis

Authors: K. L. Tooley, G. S. Howarth, K. A. Lymn, R. N. Butler

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2010

Login to get access

Abstract

Purpose

In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage.

Methods

Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration for the SBT; then applied to assess chemotherapy-induced intestinal damage. A further study was conducted to establish a SBT time-course of methotrexate-induced small intestinal damage and repair. Animals were killed at 96 or 144 h.

Results

A sucrose concentration of 0.25 g/ml was optimal (20% CV) for reproducibility and detection of intestinal damage. Maximal damage occurred at 72 h, small intestinal repair was initiated by 96 h and continued at 144 h post-MTX, as determined by the SBT and confirmed by biochemical analyses. Levels of sensitivity and specificity for the SBT were 98 and 94%, respectively.

Conclusions

The SBT is a reliable non-invasive marker of small intestinal health and damage with a high degree of sensitivity and specificity.
Literature
1.
Clarke JM, Pelton NS, Bajka BH, Howarth GS, Read LC, Butler RN (2006) Use of the sucrose breath test to assess chemotherapy-induced mucositis in the rat. Cancer Biol Ther 5:34–38PubMedCrossRef
2.
Cool JC, Dyer JL, Xian CJ, Butler RN, Geier MS, Howarth GS (2005) Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats. Growth Horm IGF Res 15:72–82CrossRefPubMed
3.
Duncan M, Grant G (2003) Review article: oral and intestinal mucositis—causes and possible treatments. Aliment Pharmacol Ther 18:853–874CrossRefPubMed
4.
Ferraris RP, Diamond J (1992) Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine. Am J Physiol Gastrointest Liver Physiol 262:G1069–G1073
5.
Ferraris RP, Diamond JM (1993) Crypt/villus site of substrate-dependent regulation of mouse intestinal glucose transporters. Proc Natl Acad Sci USA 90:5868–5872CrossRefPubMed
6.
Ferraris RP, Villenas SA, Diamond J (1992) Regulation of brush-border enzyme activities and enterocyte migration rates in mouse small intestine. Am J Physiol Gastrointest Liver Physiol 262:G1047–G1059
7.
Ferraris RP, Villenas SA, Hirayama BA, Diamond J (1992) Effect of diet on glucose transporter site density along the intestinal crypt-villus axis. Am J Physiol Gastrointest Liver Physiol 262:G1060–G1068
8.
Ghoos Y, Geypens B, Maes B, Hiele M, Vantrappen G, Rutgeerts P (1993) Breath tests in gastric emptying and transit studies: technical aspects of 13CO2-breath tests. In: Janssens J (ed) Progress in understanding and management of gastro-intestinal motility disorders. Katholieke Universiteit Leuven, Belgium, pp 169–180
9.
Gibson RJ, Keefe DMK, Thompson FM, Clarke JM, Goland GJ, Cummins AG (2002) Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci 47:2751–2757CrossRefPubMed
10.
Goda T, Takase S (1994) Dietary carbohydrate and fat independently modulate disaccharidase activities in rat jejunum. J Nutr 124:2233–2239PubMed
11.
Goda T, Yasutake H, Tanaka T, Takase S (1999) Lactase-phlorizin hydrolase and sucrase-isomaltase genes are expressed differently along the villus-crypt axis of rat jejunum. J Nutr 129:1107–1113PubMed
12.
Haycock G, Schwartz G, Wisotsky D (1978) Geometric method for measuring body surface area. J Pediatr 93:62–66CrossRefPubMed
13.
Heitlinger LA, Rossi TM, Lee P, Lebenthal E (1991) Human intestinal disaccharidase activities: correlation with age, biopsy technique, and degree of villus atrophy. J Pediatr Gastroenterol Nutr 12:204–208PubMed
14.
Howarth GS, Cool JC, Bourne AJ, Ballard FJ, Read LC (1998) Insulin-like growth factor-I (IGF-I) stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate. Growth Factors 15:279–292CrossRefPubMed
15.
Howarth GS, Tooley KL, Davidson GP, Butler RN (2006) A non-invasive method for detection of intestinal mucositis induced by different classes of chemotherapy drugs in the rat. Cancer Biol Ther 5:1189–1195PubMed
16.
Mitchell EP, Schein PS (1982) Gastrointestinal toxicity of chemotherapeutic agents. Semin Oncol 9:52–64PubMed
17.
Murch SH, Phillips AD (1996) Small intestinal biopsy. In: Walker W, Durie P, Hamilton J, Walker-Smith J, Watkins J (eds) Pediatric gastrointestinal disease, 2nd edn. B.C. Decker Inc, Philadelphia, pp 1576–1591
18.
Pelton NS, Tivey DR, Howarth GS, Davidson GP, Butler RN (2004) A novel breath test for the non-invasive assessment of small intestinal mucosal injury following methotrexate administration in the rat. Scand J Gastroenterol 39:1015–1016CrossRefPubMed
19.
20.
Sonis ST (1998) Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 34:39–43CrossRefPubMed
21.
Sonis ST, Elting LS, Keefe DMK, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025CrossRefPubMed
22.
Strohl KP, Thomas AJ, St Jean P, Schlenker EH, Koletsky RJ, Schork NJ (1997) Ventilation and metabolism among rat strains. J Appl Physiol 82:317–323CrossRefPubMed
23.
Tomas FM, Knowles SE, Owens PC, Read LC, Chandler CS, Gargosky SE, Ballard FJ (1991) Effects of full-length and truncated insulin-like growth factor-I on nitrogen balance and muscle protein metabolism in nitrogen-restricted rats. J Endocrinol 128:97–105CrossRefPubMed
24.
Tooley KL, Howarth GS, Lymn K, Lawrence A, Butler RN (2006) Oral ingestion of Streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats. Cancer Biol Ther 5:593–600CrossRefPubMed
25.
Tooley KL, Saxon BR, Webster J, Zacharakis B, McNeil Y, Davidson GP, Butler RN (2006) A novel non-invasive biomarker for assessment of small intestinal mucositis in children with cancer undergoing chemotherapy. Cancer Biol Ther 5:1275–1281CrossRefPubMed
26.
Tuovinen CG, Bender AE (1975) Some metabolic effects of prolonged feeding of starch, sucrose, fructose and carbohydrate-free diet in the rat. Nutr Metab 19:161–172CrossRefPubMed
Metadata
Title
Optimization of the non-invasive 13C-sucrose breath test in a rat model of methotrexate-induced mucositis
Authors
K. L. Tooley
G. S. Howarth
K. A. Lymn
R. N. Butler
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-009-1098-2

Other articles of this Issue 5/2010

Cancer Chemotherapy and Pharmacology 5/2010 Go to the issue

Original Article

Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression

Original Article

Antimetastatic, antineoplastic, and toxic effects of 4-hydroxycoumarin in a preclinical mouse melanoma model

Original Article

Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors

Original Article

Cetuximab-based therapy versus non-cetuximab therapy for advanced cancer: a meta-analysis of 17 randomized controlled trials

Original Article

Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol

Original Article

Co-administration of irinotecan decreases the plasma concentration of an active metabolite of amrubicin, amrubicinol in rats
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits