Modification of radiation injury by ramipril, inhibitor of angiotensin-converting enzyme, on optic neuropathy in the rat.
Inhibitors of angiotensin-converting enzyme (ACE) have been used to reduce radiation-induced normal tissue injury. The present study was carried out to determine whether ramipril, one of the inhibitors of ACE, would ameliorate radiation-induced brain damage, using a well-characterized optic neuropathy model in the rat, one of the most critical and radiosensitive structures in the brain. The brains of adult Fischer rats were irradiated stereotactically with 30 Gy using a single collimated beam. Six months after irradiation and 1.5 mg/kg day(-1) ramipril (started 2 weeks after irradiation), rats were assessed for optic nerve damage functionally, using visual evoked potential, and histologically. Results show that ramipril conferred significant modification of radiation injury, since rats receiving radiation alone showed a threefold lengthening in the mean peak latency in the visual evoked potential, whereas 75% of rats receiving radiation followed by ramipril had evoked potentials that resembled those of normal untreated control rats. The histology of irradiated and ramipril-treated optic nerves appeared nearly normal, while there was significant demyelination in both optic nerves of irradiated rats. The study represents the first demonstration of prophylaxis of radiation injury by a carboxyl-containing ACE inhibitor, providing a pharmacological strategy designed to reduce radiation-induced normal tissue damage.
Kim
Jae Ho
JH
Departments of Radiation Oncology, Neurosurgery and Medicine, Henry Ford Health System, Detroit, MI 48202, USA. jkim1@hfhs.org
Brown
Stephen L
SL
Kolozsvary
Andrew
A
Jenrow
Kenneth A
KA
Ryu
Samuel
S
Rosenblum
Mark L
ML
Carretero
Oscar A
OA
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005074:Evoked Potentials, Visual / Q000528:radiation effects*; D008297:Male; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D017257:Ramipril / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D011837:Radiation-Protective Agents; D017257:Ramipril