Angiotensin converting enzyme inhibitor captopril does not prevent acute gastrointestinal radiation damage in the rat

Moulder, John E.; Fish, Lawrence

doi:10.1002/(sici)1520-6823(1997)5:2<50::aid-roi2>3.0.co;2-i

Cited by 16 publications

(5 citation statements)

References 16 publications

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“…In both the vehicle- and Captopril-treated groups, circulating lymphocytes remained lower for up to 2 months post-irradiation, whereas platelets returned to normal within 1 month. This is in agreement with Moulder and Fish who showed that Captopril did not prevent acute Gl radiation-induced damage [49]. …”

Section: Resultssupporting

confidence: 92%

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

et al. 2002

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Background: Absorption of water and Na + in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na + diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a postirradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated.

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Section: Resultssupporting

confidence: 92%

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

et al. 2002

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“…While there could be some overlap in time between the lung and renal morbidity, they can be distinguished in individual rats based on whether euthanasia was based on pneumonitis or nephropathy criteria. Enalapril had no effect on the early (ARS) phase, which is not unexpected because enalapril did not start until 5 days after PBI, and we have previously shown that ACEi do not mitigate GI (11) or hematological (12) radiation-induced injury in this model. Thereafter, both the enalapril fixed-dose and the enalapril escalated-dose groups showed significant mitigation benefit compared to irradiated rats not receiving drug (Table 1).…”

Section: Resultssupporting

confidence: 50%

Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury

2016

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Angiotensin-converting enzyme inhibitors (ACEi) are effective mitigators of radiation nephropathy. To date, their experimental use has been in fixed-dose regimens. In clinical use, doses of ACEi and other medication may be escalated to achieve greater benefit. We therefore used a rodent model to test the ACEi enalapril as a mitigator of radiation injury in an escalating-dose regimen. Single-fraction partial-body irradiation (PBI) with one hind limb out of the radiation field was used to model accidental or belligerent radiation exposures. PBI doses of 12.5, 12.75 and 13 Gy were used to establish multi-organ injury. One third of the rats underwent PBI alone, and two thirds of the rats had enalapril started five days after PBI at a dose of 30 mg/l in the drinking water. When there was established azotemic renal injury enalapril was escalated to a 60 mg/l dose in half of the animals and then later to a 120 mg/l dose. Irradiated rats on enalapril had significant mitigation of combined pulmonary and renal morbidity and had significantly less azotemia. Dose escalation of enalapril did not significantly improve outcomes compared to fixed-dose enalapril. The current data support use of the ACEi enalapril at a fixed and clinically usable dose to mitigate radiation injury after partial-body radiation exposure.

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“…We do not observe an effect of ACEIs/ARBs on radiation-related toxicities in the current study. However, prior preclinical studies have also not observed an effect of these medications on the gastrointestinal side effects of radiation, 36 which are likely to predominate in our patient population.…”

Section: Discussionmentioning

confidence: 76%

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers

Morris

Saha

Magnuson

et al. 2016

Cancer

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BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. METHODS: One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen's Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. RESULTS: Among patients taking ACEIs/ARBs in the UW data set, a significant 3-fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P 5 .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold-increased pCR rate (24% vs 12%, P 5 .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06-7.82; P < .001). CONCLUSIONS: The incidental use of ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment. Cancer 2016;122:2487-95.

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Angiotensin converting enzyme inhibitor captopril does not prevent acute gastrointestinal radiation damage in the rat

Cited by 16 publications

References 16 publications

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers

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