Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile.
Chemotherapy-induced diarrhoea is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. Irinotecan is linked with severe mucositis and diarrhoea, the mechanisms of which remain poorly understood. Bacterial beta-glucuronidase is thought to be involved in the metabolism of irinotecan, implicating the intestinal flora. Intestinal mucins may also be implicated in the development of chemotherapy-induced diarrhoea. Rats were treated with 200 mg/kg of irinotecan and killed at 96, 120 and 144 h. The rats were monitored for diarrhoea. Pathology and immunohistochemical staining was performed. The samples were cultured and faecal DNA was analysed using real-time polymerase chain reaction. Severe diarrhoea was observed from 72 to 96 h. A decrease in body mass was also observed after treatment. Significant changes in goblet cell numbers (both complete and cavitated cells) were observed in the small and large intestines. Changes in MUC gene expression were observed in the small intestine only. Modifications were observed to the intestinal flora profile, especially Escherichia coli, and an increase in the expression of beta-glucuronidase was detected. In conclusion, irinotecan-induced diarrhoea may be caused by an increase in some beta-glucuronidase-producing bacteria, especially E. coli, exacerbating the toxicity of active metabolites. Accelerated mucous secretion and mucin release may also contribute to the delayed onset of diarrhoea.
Stringer
Andrea M
AM
Department of Medical Oncology, Royal Adelaide Hospital, South Australia, Australia. andrea.stringer@imvs.sa.gov.au
Gibson
Rachel J
RJ
Bowen
Joanne M
JM
Logan
Richard M
RM
Ashton
Kimberly
K
Yeoh
Ann S J
AS
Al-Dasooqi
Noor
N
Keefe
Dorothy M K
DM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005243:Feces / Q000382:microbiology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D000077146:Irinotecan; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009077:Mucins / Q000378:metabolism; D052016:Mucositis / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051381:Rats
D000972:Antineoplastic Agents, Phytogenic; D009077:Mucins; D000077146:Irinotecan; D005966:Glucuronidase; D002166:Camptothecin