title: An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.
abstract: Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice. A single-hit, multi-target crypt survival curve showed a significant increase in crypt progenitors in irradiated mice treated with AA-ORS for six days (8.8 ± 0.4) compared to the saline-treated group (6.1 ± 0.3; P < 0.001) without a change in D0(4.8 ± 0.1 Gy). The Dqvalues increased from 8.8 ± 0.4 Gy to 10.5 ± 0.5 Gy with AA-ORS treatment (P < 0.01), indicating an increased radiation tolerance of 1.7 Gy. We also found that AA-ORS treatment (1) increased Lgr5+, without altering Bmi1 positive cells; (2) increased levels of proliferation markers (Ki-67, p-Erk, p-Akt and PCNA); (3) decreased apoptosis markers, such as cleaved caspase-3 and Bcl-2; and (4) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane. This study shows that AA-ORS increased villus height and improved electrolyte and nutrient absorption.
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Reshu
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Vaught
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Grosche
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Cancer and Genetics Research Complex, 2033 Mowry Road, Box 103633, Gainesville, FL 32610, USA.
authors.forename: Sadasivan
authors.initials: S
authors.lastname: Vidyasagar
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015532:Rehydration Solutions / Q000737:chemistry / Q000494:pharmacology*; D051269:Sodium-Glucose Transporter 1 / Q000096:biosynthesis; D000074083:Sodium-Hydrogen Exchanger 3 / Q000096:biosynthesis
chemical_list: D000596:Amino Acids; D015532:Rehydration Solutions; C495675:Slc5a1 protein, mouse; C000613386:Slc9a3 protein, mouse; D051269:Sodium-Glucose Transporter 1; D000074083:Sodium-Hydrogen Exchanger 3