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

Ryu, Samuel; Kolozsvary, Andrew; Jenrow, Kenneth A.; Brown, Stephen L.; Kim, Jae Ho

doi:10.1007/s11060-006-9256-4

Cited by 46 publications

(35 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Modulation of the RAS has been shown previously to mitigate the severity of radiation-induced CNS injury (29, 30). Chronic administration of the ACEI, ramipril, initiated two weeks after stereotactic irradiation of the rat brain with a single dose of 30 Gy, was associated with a reduction in the severity of functional and histopathologic markers of optic neuropathy assessed 6 months post-irradiation (29).…”

Section: Discussionmentioning

confidence: 98%

The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation–Induced Cognitive Impairment

Robbins

Payne

Tommasi

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

Purpose-We hypothesized that administration of the angiotensin type 1 (AT 1 ) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-Administration of L-158,809 prior to, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks post-irradiation. Moreover, giving L-158,809 prior to, during, and for only 5 weeks post-irradiation ameliorated the significant cognitive impairment observed 26 weeks post-irradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks post-irradiation, respectively. Methods and Materials-Groups NIH Public AccessConclusions-Administering L-158,809 prior to, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks post-irradiation. These findings offer the promise of improving the quality of life for brain tumor patients.

show abstract

Section: Discussionmentioning

confidence: 98%

The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation–Induced Cognitive Impairment

Robbins

Payne

Tommasi

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

show abstract

“…At doses (on a mg/m 2 /day basis) approved by the FDA for use in humans, captopril improves vascular, functional and structural derangements that develop in the rat lung by 8 weeks after a single dose of radiation. Inhibition of ACE is also able to mitigate radiation nephropathy (7), radiation injury to the central nervous system (29) and to lower the incidence of radiation-induced neoplasms (30). Our studies indicate that initiation of captopril therapy after a delay of 1 week following injury also has mitigating properties.…”

Section: Discussionmentioning

confidence: 99%

Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

Ghosh¹,

Zhang²,

Fish³

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

100

113

View full text Add to dashboard Cite

Purpose To find mitigators of pneumonitis induced by moderate doses of thoracic radiation (10–15 Gy). Materials and Methods Unanesthetized WAG/RijCmcr female rats received single doses of X-irradiation (10, 12 or 15 Gy at 1.615 Gy/minute) to the thorax. Captopril (an angiotensin converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating breathing rate, ex vivo vascular reactivity and histopathology. Survival analysis was undertaken on all animals except those scheduled for sacrifice. Results Survival following a dose of 10 Gy to the thorax was not different from unirradiated rats up to one year. Survival decreased to less than 50%, by 45 weeks after 12 Gy and by 8–9 weeks after 15 Gy. Captopril (17–56 mg/kg/day) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity and histopathological evidence of injury. Radiation-induced increases in breathing rate were prevented even if captopril was started 1 week following irradiation or if it was discontinued after 5 weeks. Losartan, though effective in reducing mortality was not as efficacious as captopril in mitigating radiation-induced increases in breathing rate or altered vasoreactivity. Conclusions In rats, a moderate thoracic dose of radiation induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was commenced 1 week after irradiation or if discontinued after 5 weeks following exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.

show abstract

“…We have demonstrated mitigation of radiation-induced neurotoxicity by the prodrug ACE inhibitor ramipril in an animal model. 23 A translational clinical trial is in progress. The biological effectiveness of the spinal cord dose used in spine radiosurgery may be clinically below the widely accepted spinal cord tolerance dose of 45 to 50 Gy, 24 or the more recent estimate of 57 to 61 Gy in conventional fractionation, 25 which may cause a 5% complication rate in 5 years.…”

Section: Discussionmentioning

confidence: 99%

Partial volume tolerance of the spinal cord and complications of single‐dose radiosurgery

Ryu

Jin

et al. 2006

Cancer

Self Cite

233

150

View full text Add to dashboard Cite

BACKGROUND.Spine radiosurgery causes a rapid dose fall‐off within the spinal cord. The tolerance of partial volume of the spinal cord may determine the extent of clinical application. The study analyzed the partial volume tolerance of the human spinal cord to single fraction radiosurgery.METHODS.A total of 230 lesions with spine metastases in 177 patients were treated with radiosurgery with single fraction of 8 to 18 Gy, prescribed to the 90% isodose line that encompassed the target volume. Spinal cord volume was defined as 6 mm above and below the radiosurgery target volume. Spinal cord dose was calculated from the radiation dose/spinal cord volume histogram and correlated with clinical/neurological status and radiographic studies. Median follow‐up was 6.4 months (range, 0.5–49 months). The 1‐year survival rate was 49%.RESULTS.The average spinal cord volume defined at the treated spinal segment was 5.9 ± 2.2 mL. The average dose to the 10% spinal cord volume was 9.8 ± 1.5 Gy, calculated from the dose‐volume histogram in the group of 18 Gy prescribed dose. The spinal cord volume that received higher than 80% of the prescribed dose was 0.07 ± 0.10 mL, which represented 1.3 ± 1.8% of the cord volume. Among the 86 patients who survived longer than 1 year there was 1 case of radiation‐induced cord injury after 13 months of radiosurgery. There were no other cases of spinal cord sequelae.CONCLUSIONS.Whereas the maximum spinal cord tolerance to single‐dose radiation is not known, partial volume tolerance of the human spinal cord is at least 10 Gy to 10% of the spinal cord volume defined as 6 mm above and below the radiosurgery target. Cancer 2007;109:628–636. © 2006 American Cancer Society.

show abstract

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

Abstract: 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.

Cited by 46 publications

References 24 publications

The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation–Induced Cognitive Impairment

The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation–Induced Cognitive Impairment

Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

Partial volume tolerance of the spinal cord and complications of single‐dose radiosurgery

Contact Info

Product

Resources

About