TY - JOUR
T1 - Pyridoxamine protects intestinal epithelium from ionizing radiation-induced apoptosis
AU - Thotala, Dinesh
AU - Chetyrkin, Sergei
AU - Hudson, Billy
AU - Hallahan, Dennis
AU - Voziyan, Paul
AU - Yazlovitskaya, Eugenia
N1 - Funding Information:
This work has been supported by Grants DK66415 (P.V.), DK65138 (B.H.), and CA89674 (D.H.) from the National Institutes of Health and by research grants from the Pardee Foundation (E.Y.) and Whitmer Family Foundation (D.H.).
PY - 2009/9/15
Y1 - 2009/9/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Free radicals
KW - Gastrointestinal tract
KW - Ionizing radiation
KW - Pyridoxamine
KW - Radiation toxicity
KW - Radioprotection
KW - Reactive carbonyl species
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=68349128509&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2009.06.020
DO - 10.1016/j.freeradbiomed.2009.06.020
M3 - Article
C2 - 19540915
AN - SCOPUS:68349128509
SN - 0891-5849
VL - 47
SP - 779
EP - 785
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -