Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor ramipril: importance of ramipril dose and treatment time.

Abstract:

PURPOSE:Radiation-induced optic nerve damage was reduced by ramipril, a prodrug angiotensin-converting enzyme inhibitor (ACEI). This study was to determine the optimum dose and administration time of ramipril for mitigating radiation-induced optic neuropathy. MATERIALS AND METHOD:Adult Fischer 344 male rats were treated with a single dose radiation 30 Gy by using radiosurgical technique. After irradiation, the animals were randomly assigned into groups of different ramipril doses and administration time; control (no treatment), radiation alone, radiation+ramipril in different doses and starting times of drug. Ramipril was given 0.5-1.5 mg/kg/day and AT1R blocker Losartan 20 mg/kg/day in drinking water for 180 days. Functional endpoint with visual evoked potential (VEP) and anatomical endpoint with gross and histological analysis with immunohistochemical (IHC) stain were used. RESULTS:Normal VEP measurements in un-irradiated rats were 46.2+/-7.9 ms. There was no change of VEP value until 4 months, but was lengthened to 188.1+/-58.7 ms at 6 months after radiation. By ramipril treatment with the dose of 1.5 mg starting at 2 weeks after radiation, VEP was significantly shortened to 105.7+/-88.5 ms at 6 months. Gross and microscopic structure of the irradiated optic nerve was well preserved in the ramipril-treated group. CONCLUSION:Ramipril can mitigate the radiation-induced optic nerve damage and preserve the functional integrity of the nerve. The results support early treatment with a high dose of ramipril after radiation.

journal_name

J Neurooncol

authors

Ryu S,Kolozsvary A,Jenrow KA,Brown SL,Kim JH

doi

10.1007/s11060-006-9256-4

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

119-24

issue

2

eissn

0167-594X

issn

1573-7373

journal_volume

82

pub_type

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