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Renin-angiotensin system blockers and modulation of radiation-induced brain injury.

Abstract
Radiation-induced brain injury remains a major cause of morbidity in cancer patients with primary or metastatic brain tumors. Approximately 200,000 individuals/year are treated with fractionated partial or whole-brain irradiation, and > half will survive long enough (≤6 months) to develop radiation-induced brain injury, including cognitive impairment. Although short-term treatments have shown efficacy, no long-term treatments or preventive approaches are presently available for modulating radiation-induced brain injury. Based on previous preclinical studies clearly demonstrating that renin-angiotensin system (RAS) blockers can modulate radiation-induced late effects in the kidney and lung, we and others hypothesized that RAS blockade would similarly modulate radiation-induced brain injury. Indeed, studies in the last 5 years have shown that both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor antagonists (AT(1)RAs) can prevent/ameliorate radiation-induced brain injury, including cognitive impairment, in the rat. The mechanistic basis for this RAS blocker-mediated effect remains the subject of ongoing investigations. Putative mechanisms include, i] blockade of Ang II/NADPH oxidase-mediated oxidative stress and neuroinflammation, and ii] a change in the balance of angiotensin (Ang) peptides from the pro-inflammatory and pro-oxidative Ang II to the anti-inflammatory and anti-oxidative Ang-1-7). However, given that both ACEIs and AT(1)RAs are 1] well-tolerated drugs routinely prescribed for hypertension, 2] exhibit some antitumor properties, and 3] can prevent/ameliorate radiation-induced brain injury, they appear to be ideal drugs for future clinical trials, offering the promise of improving the quality of life of brain tumor patients receiving brain irradiation.
AuthorsM E Robbins, W Zhao, M A Garcia-Espinosa, D I Diz
JournalCurrent drug targets (Curr Drug Targets) Vol. 11 Issue 11 Pg. 1413-22 (Nov 2010) ISSN: 1873-5592 [Electronic] United Arab Emirates
PMID20583976 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
Topics
  • Angiotensin Receptor Antagonists (pharmacology, therapeutic use)
  • Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
  • Animals
  • Brain (radiation effects)
  • Brain Injuries (drug therapy, etiology, prevention & control)
  • Brain Neoplasms (radiotherapy)
  • Humans
  • Radiation Injuries (drug therapy, prevention & control)
  • Renin-Angiotensin System (drug effects)

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