Nutritional benefits of enteral alanyl-glutamine supplementation on rat small intestinal damage induced by cyclophosphamide.
BACKGROUND
Glutamine is the principal fuel used by the small intestine. Although the parental administration of glutamine promotes intestinal mucosal growth, it is controversial whether enteral glutamine is effective against small intestinal damage caused by chemotherapy. To further evaluate the benefits of enteral supplementation, peptide and amino acid transporter functions must be considered.


METHODS
Rats were given cyclophosphamide (CPM) intraperitoneally (300 mg/kg). Expression of the amino acid transporter, B0 and peptide transporter (PepT1) in the jejunal mucosa was initially examined by northern blot analysis. Rats received a bolus oral supplement of an alanine (1.22 g/kg/day) plus glutamine (2.0 g/kg/day) mixture, alanyl-glutamine (2.972 g/kg/day) or saline as a control, for 7 days after CPM administration.


RESULTS
Levels of B0 mRNA remained unchanged at both 3 and 7 days after CPM administration. Conversely, PepT1 mRNA increased significantly after CPM administration, and reached 200% of the initial level 7 days later. In rats given alanyl-glutamine, the mucosal wet weight and protein content increased significantly with increasing villus height at 3 and 7 days, compared with the alanine plus glutamine mixture. The plasma glutamine concentration in the alanyl-glutamine group, but not the alanine plus glutamine mixture group, increased significantly compared with that in the saline group.


CONCLUSIONS
Enteral supplementation with an alanyl-glutamine but not alanine plus glutamine mixture prevents intestinal damage, as demonstrated by increased peptide transport expression and an elevated plasma glutamine concentration after CPM administration.
Satoh
Jin
J
Division of Gastroenterology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, Japan.
Tsujikawa
Tomoyuki
T
Fujiyama
Yoshihide
Y
Bamba
Tadao
T
D000409:Alanine / Q000097:blood / Q000187:drug effects; D026905:Amino Acid Transport Systems / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D015820:Cadherins; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D019587:Dietary Supplements; D004151:Dipeptides / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004750:Enteral Nutrition; D005973:Glutamine / Q000097:blood / Q000187:drug effects; D007410:Intestinal Diseases / Q000139:chemically induced*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D026901:Membrane Transport Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D026905:Amino Acid Transport Systems; D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D015820:Cadherins; D002352:Carrier Proteins; C490586:Cdh17 protein, rat; D004151:Dipeptides; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C067802:intestinal peptide-proton cotransporter; D005973:Glutamine; D003520:Cyclophosphamide; D000409:Alanine; C054122:alanylglutamine