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Intestinal response to myeloablative chemotherapy in piglets
Peter L Pontoppidan1, René L Shen, Bodil L Petersen
1Department of Nutrition, Exercise and Sports, 30 Rolighedsvej, 1958 Frederiksberg C, Denmark.
Experimental Biology and Medicine (Maywood, N.J.)
|December 6, 2013
Summary
Milk-fed piglets effectively model chemotherapy-induced gastrointestinal toxicity after busulfan (Bu) and cyclophosphamide (Cy) conditioning for hematopoietic stem cell transplantation (HSCT). This piglet model shows clinical signs and intestinal damage similar to pediatric patients, aiding research into toxicity and interventions.
Area of Science:
- Veterinary Medicine
- Gastroenterology
- Oncology
Background:
- Chemotherapy-induced myeloablation before hematopoietic stem cell transplantation (HSCT) can cause severe oral and gastrointestinal (GI) toxicity.
- Current understanding of GI toxicity is limited, particularly in human pediatric populations, with most data from rodent models.
Purpose of the Study:
- To evaluate milk-fed piglets as a clinically relevant model for chemotherapy-induced GI toxicity.
- To investigate the dose-response relationship of a standard busulfan (Bu) and cyclophosphamide (Cy) conditioning regimen in piglets prior to HSCT.
Main Methods:
- Two studies were conducted using three-day-old piglets. Study 1 established dose-response relationships for Bu and Cy regimens. Study 2 utilized the myeloablative regimen from Study 1 (Treatment A) to assess clinical signs and GI toxicity.
- Histological analysis of bone marrow, spleen, and intestinal tissues was performed. Clinical signs, body weight, and blood chemistry were monitored. Intestinal villus height and brush-border enzyme activities were measured.
Main Results:
- The myeloablative Bu-Cy regimen (Treatment A) resulted in total bone marrow aplasia.
- Piglets exhibited reduced spleen and intestinal weights, dehydration, sepsis, and pneumonia. Oral mucositis was observed in 4/9 piglets.
- Intestinal villus height and brush-border enzyme activities were significantly reduced, especially in the proximal intestine. Elevated blood iron levels were noted, with no consistent changes in tissue cytokines or most blood chemistry values.
Conclusions:
- A myeloablative busulfan and cyclophosphamide regimen in piglets produces clinical signs and GI toxicity comparable to pediatric patients undergoing HSCT.
- Piglets serve as a valuable preclinical model for studying chemotherapy-induced toxicity and evaluating potential dietary or medical interventions.
