title: Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat.
abstract: Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive ( 13) C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p < 0.05) compared to saline and TH-4 control rats. TH-4 treatment did not result in tumor progression (p > 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.
authors.affiliation: Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service (CYWHS), North Adelaide, Adelaide, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Tooley
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Lymn
authors.forename: Andrew
authors.initials: A
authors.lastname: Lawrence
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D004435:Eating; D005260:Female; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D052016:Mucositis / Q000139:chemically induced / Q000517:prevention & control*; D019936:Probiotics / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D048249:Streptococcus thermophilus
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate