title: Pyridoxamine protects intestinal epithelium from ionizing radiation-induced apoptosis.
abstract: Reactive oxygen species (ROS) and reactive carbonyl species (RCS) are the major causes of biological tissue damage during exposure to ionizing radiation (IR). The existing strategies to protect normal tissues from the detrimental effects of IR suffer from several shortcomings including highly toxic side effects, unfavorable administration routes, and low efficacy. These shortcomings emphasize a need for radioprotective treatments that combine effectiveness with safety and ease of use. In this paper, we demonstrate that pyridoxamine, a ROS and RCS scavenger with a very favorable safety profile, can inhibit IR-induced gastrointestinal epithelial apoptosis in cell culture and in an animal model. Pyridoxamine was more effective at protecting from radiation-induced apoptosis than amifostine, a synthetic thiol compound and the only FDA-approved radioprotector. We suggest that pyridoxamine has potential as an effective and safe radioprotective agent.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Thotala
authors.forename: Sergei
authors.initials: S
authors.lastname: Chetyrkin
authors.forename: Billy
authors.initials: B
authors.lastname: Hudson
authors.forename: Dennis
authors.initials: D
authors.lastname: Hallahan
authors.forename: Paul
authors.initials: P
authors.lastname: Voziyan
authors.forename: Eugenia
authors.initials: E
authors.lastname: Yazlovitskaya
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011733:Pyridoxamine / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D011733:Pyridoxamine; D004999:Amifostine