Nutritional supplementation with transforming growth factor-beta, glutamine, and short chain fatty acids minimizes methotrexate-induced injury.
OBJECTIVE
Gastrointestinal (GI) damage caused by methotrexate (MTX) results in mucosal injury, bacterial invasion, and activation of an immune system that is reduced in function. Diets enriched with glutamine, short chain fatty acids (SCFAs), and transforming growth factor (TGF)-beta have demonstrated decreased infection, weight loss, and GI damage in Crohn disease. We, therefore, sought to study the cytoprotective effects of a diet enriched in glutamine, TGF-beta, and SFCAs (Modulen) in Fischer 344 rats exposed to MTX.


METHODS
Rats were divided into five groups: two receiving normal saline and three receiving MTX and fed either normal chow, Modulen supplemented chow starting with the first MTX dose, or Modulen supplemented chow beginning 3 days before MTX injection. Rats were weighed daily. On day 5, albumin and bicarbonate levels were drawn, and rats were killed for examination of their intestinal mucosa by a pathologist unaware of groupings.


RESULTS
Rats pretreated with Modulen supplemented chow maintained weight (2.6 vs, 12.3 g weight loss), albumin levels (3.13 vs, 2.43 mg/dL), and bicarbonate levels (23.8 vs. 18.1 mg/dL) as compared with rats fed normal chow throughout MTX treatment (P < 0.05). Pretreatment with Modulen also protected against crypt cell loss, villus atrophy, crypt abscesses, crypt/villus ratio, and overall histologic damage (P < 0.05).


CONCLUSIONS
When administered before and during MTX treatment, Modulen supplementation provided statistically significant protection against weight loss, hypoalbuminemia, acidosis, and GI damage in a rat model. Future animal research of Modulen's protective effects with other chemotherapeutic agents is needed before human trials.
Harsha
Wendy T F
WT
Department of Pediatrics, Madigan Army Medical Center, Tacoma, Washington 98431, USA. wendy.harsha@nw.amedd.army.mil
Kalandarova
Ellina
E
McNutt
Patrick
P
Irwin
Robert
R
Noel
James
J
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D019587:Dietary Supplements; D005232:Fatty Acids, Volatile / Q000008:administration & dosage* / Q000627:therapeutic use; D005973:Glutamine / Q000008:administration & dosage* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008727:Methotrexate / Q000633:toxicity*; D052016:Mucositis / Q000139:chemically induced / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D005232:Fatty Acids, Volatile; D016212:Transforming Growth Factor beta; D005973:Glutamine; D008727:Methotrexate