Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet: comparative study with a casein-containing diet.
Effects of two clinically used liquid diets on toxicity and antitumor activity of methotrexate (MTX) were investigated in Sprague-Dawley (SD) rats and tumor-bearing mice, respectively. Diets tested were commercially available formulas enriched either with soybean and omega-3 fatty acids or with casein. The soybean-containing diet offered significant protection against MTX toxicity in rats compared with the casein-containing diet, completely alleviating MTX-induced anorexia, diarrhea, and weight loss, when ingested as the sole diet and fed 7 days prior to and 7 days following intraperitoneal MTX injection. As a result, 90% of rats were alive on soybean-containing diet while all rats were dead on casein-containing diet. Histologic examination of the small intestine of MTX-treated rats revealed that the soybean-containing diet significantly prevented loss of mucosal villus tips compared to the casein-containing diet. Pharmocokinetic examination indicated that plasma MTX concentrations were similar for rats in the two diet-defined groups. No significant differences were observed between diets in survival of mice injected with L1210 mouse leukemia cells and subsequently with MTX. Thus the soybean-containing diet appeared to be superior to the casein-containing diet in preventing gastrointestinal toxicity while preserving antitumor activity. A soybean diet enriched in omega-3 fatty acids may be a useful adjunct to MTX treatment of human cancers.
Mitsugi
Kenji
K
First Department of Internal Medicine, and Department of Medicine and Biosystemic Science, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
Nakamura
Tsuyoshi
T
Kashiwabara
Norio
N
Ariyama
Hiroshi
H
Tanaka
Risa
R
Baba
Eishi
E
Nakamura
Minoru
M
Harada
Mine
M
Nakano
Shuji
S
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002364:Caseins; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D008871:Microvilli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D030262:Soybean Proteins / Q000627:therapeutic use*; D013025:Glycine max
D002364:Caseins; D015525:Fatty Acids, Omega-3; D030262:Soybean Proteins; D008727:Methotrexate