Transforming Growth Factor-beta2 protects the small intestine during methotrexate treatment in rats possibly by reducing stem cell cycling.
During chemo- and radiation therapy, the balance between epithelial cell proliferation, differentiation, and cell death at the villus tip is disrupted by premature death of dividing epithelial cells. This will subsequently lead to the onset of mucosal barrier injury in the whole gastrointestinal tract. Up till now there is no validated method to treat side effects occurring due to therapy. An approach to manage this side effect might be to reversibly arrest growth of epithelial stem cells during therapy using Transforming Growth Factor-beta2. A Transforming Growth Factor-beta2 enriched fraction prepared from bovine milk was shown to protect small intestinal epithelial cells against cell cycle specific chemotherapeutic agents by arresting the cells in G1-phase. Secondly, in a rat model for induced small intestinal damage, oral supplementation of rats exposed to methotrexate with the Transforming Growth Factor-beta2 enriched fraction significantly reduced the chemotherapy-associated weight loss and ileal villus atrophy by reducing cell proliferation in the normal stem cell population. Thus oral supplementation with a bovine milk fraction enriched for Transforming Growth Factor-beta2 attenuated the side effects of chemotherapy in the small intestine in rats.
van't Land
B
B
Numico-Research, Department of Condition and Disease Specific Research, Bosrandweg 20, PO Box 6700 CA Wageningen, The Netherlands.
Meijer
H P
HP
Frerichs
J
J
Koetsier
M
M
Jager
D
D
Smeets
R L
RL
M'Rabet
L
L
Hoijer
M
M
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001284:Atrophy; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology*; D008727:Methotrexate / Q000009:adverse effects*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2; D015431:Weight Loss
D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D008727:Methotrexate