An amino acid mixture mitigates radiation-induced gastrointestinal toxicity.
Electrolyte and nutrient absorption occur in villous epithelial cells. Radiation often results in reduced electrolyte and nutrient absorption, which leads to gastrointestinal toxicity. Therefore, the authors studied: (1) radiation-induced changes in glucose and amino acid absorption across ileal tissues and (2) the effect of amino acid mixtures on absorptive capacity. NIH Swiss mice were irradiated (0, 1, 3, 5, or 7 Gy) using a ¹³⁷Cs source at 0.9 Gy min⁻¹. Transepithelial short circuit current (I(sc)), dilution potential, and isotope flux determinations were made in Ussing chamber studies and correlated to plasma endotoxin and IL-1β levels. Amino acids that increased electrolyte absorption and improved mucosal barrier functions were used to create a mitigating amino acid mixture (MAAM). The MAAM was given to mice via gastric gavage; thereafter, body weight and survival were recorded. A significant decrease in basal and glucose-stimulated sodium absorption occurred after 0, 1, 3, 5, and 7 Gy irradiation. Ussing chamber studies showed that paracellular permeability increased following irradiation and that the addition of glucose resulted in a further increase in permeability. Following irradiation, certain amino acids manifested decreased absorption, whereas others were associated with increased absorption. Lysine, aspartic acid, glycine, isoleucine, threonine, tyrosine, valine, tryptophan, and serine decreased plasma endotoxins were selected for the MAAM. Mice treated with the MAAM showed increased electrolyte absorption and decreased paracellular permeability, IL-1β levels, and plasma endotoxin levels. Mice treated with MAAM also had increased weight gain and better survival following irradiation. The MAAM has immediate potential for use in mitigating radiation-induced acute gastrointestinal syndrome.
*Department of Radiation Oncology, University of Florida Shands Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610.
Liangjie
L
Yin
Pooja
P
Vijaygopal
Rejeesh
R
Menon
Lauren A
LA
Vaught
Mei
M
Zhang
Lurong
L
Zhang
Paul
P
Okunieff
Sadasivan
S
Vidyasagar
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004731:Endotoxins / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D005947:Glucose / Q000494:pharmacology; D053583:Interleukin-1beta / Q000097:blood; D007408:Intestinal Absorption / Q000187:drug effects / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D010539:Permeability / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000737:chemistry* / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects / Q000528:radiation effects
D000596:Amino Acids; D004731:Endotoxins; D053583:Interleukin-1beta; D011837:Radiation-Protective Agents; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D005947:Glucose