Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis

Scand J Gastroenterol. 2013 Aug;48(8):959-68. doi: 10.3109/00365521.2013.812142.

Abstract

Background: Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined.

Aims: The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin.

Methods: Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment.

Results: Body weight was significantly decreased by doxorubicin compared with normal controls (p < 0.05). Histological parameters, such as crypt depth and villus height, were also significantly decreased by doxorubicin. TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit.

Conclusions: The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects*
  • Biomarkers / metabolism
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects*
  • Female
  • Ileum / metabolism
  • Ileum / pathology
  • Injections, Intraperitoneal
  • Jejunum / metabolism
  • Jejunum / pathology
  • Mucositis / chemically induced
  • Mucositis / metabolism
  • Mucositis / pathology
  • Mucositis / therapy*
  • Peroxidase / metabolism
  • Probiotics / therapeutic use*
  • Random Allocation
  • Rats
  • Streptococcus thermophilus*
  • Treatment Outcome
  • Weight Loss

Substances

  • Antibiotics, Antineoplastic
  • Biomarkers
  • Doxorubicin
  • Peroxidase