A non-invasive method for detection of intestinal mucositis induced by different classes of chemotherapy drugs in the rat.
BACKGROUND
The Sucrose Breath Test (SBT) is a simple noninvasive technique for the detection of small intestinal mucositis.


OBJECTIVE
We utilised rat models of intestinal mucositis induced by different classes of chemotherapeutic agents to broaden application of the SBT.


METHODS
Mucositis was induced in rats by injection of Doxorubicin (Dox), Etoposide (Etop), Irinotecan (Irin), or Cyclophosphamide (Cy) and Etop in combination (Cy+Etop). The SBT was carried out following sucrose gavage, 72 h after chemotherapy. At kill, intestinal tissues were collected for mucositis assessments.


RESULTS
SBT for controls was 16.0 +/- 0.6% (mean +/- SEM) cumulative dose at 90 min. Irin, Doxo, Etop, and Cy+Etop significantly decreased the SBT to 53%, 43%, 32% and 30% of saline control values, respectively (p < 0.01) whilst sucrase activity was correspondingly decreased to 60%, 36%, 14% and 2%. There was good concordance with histological mucositis severity in the jejunum, with median scores of 11, 19, 28 and 27. Correlations between SBT, sucrase activity, and histological severity score yielded r(2) values of 0.82.


CONCLUSIONS
The SBT detected mucositis induced by the alkylating agent, anthracycline and DNA-topoisomerase inhibitor classes, facilitating the detection of small intestinal dysfunction, providing a further means to screen newly-developed drugs for intestinal side-effects.
Howarth
Gordon S
GS
Centre for Pediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, Adelaide, Australia.
Tooley
Katie L
KL
Davidson
Geoffrey P
GP
Butler
Ross N
RN
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D001944:Breath Tests / Q000379:methods*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D004264:DNA Topoisomerases, Type I / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005047:Etoposide / Q000633:toxicity; D005260:Female; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D000077146:Irinotecan; D052016:Mucositis / Q000139:chemically induced* / Q000175:diagnosis*; D051381:Rats; D013393:Sucrase / Q000378:metabolism; D013395:Sucrose / Q000032:analysis* / Q000378:metabolism; D059004:Topoisomerase I Inhibitors
D018906:Antineoplastic Agents, Alkylating; D059004:Topoisomerase I Inhibitors; D013395:Sucrose; D005047:Etoposide; D000077146:Irinotecan; D004317:Doxorubicin; D003520:Cyclophosphamide; D013393:Sucrase; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin