Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

Hosseinimehr, Seyed Jalal; Mahmoudzadeh, Aziz; Akhlagpour, Shahram

doi:10.1002/cbf.1311

Cited by 11 publications

(4 citation statements)

References 23 publications

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“…Captopril has been proposed to function as an antioxidant [37], a free radical scavenger [38], and as an inhibitor of other proteases such as matrix metalloproteinases [39]. Captopril and other ACE inhibitors when administered postirradiation have been shown to modify a variety of late radiation-induced tissue injuries in the kidney, lung, skin, and heart [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation

Davis

Landauer²,

Mog³

et al. 2010

Experimental Hematology

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Objective Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of ACE inhibitors on radiation-induced injury to the hematopoietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation-induced hematopoietic injury. Methods C57BL/6 mice were either sham irradiated or were exposed to 60Co total body irradiation (0.6 Gy/min). Captopril was provided in the water for different time periods relative to irradiation. Results In untreated mice, the survival rate from 7.5 Gy was 50% at 30 days postirradiation. Captopril treatment for 7 days prior to irradiation resulted in radiosensitization with 100% lethality and a rapid decline of mature blood cells. In contrast, captopril treatment beginning 1 hour postirradiation and continuing for 30 days resulted in 100% survival, with improved recovery of mature blood cells and multilineage hematopoietic progenitors. In nonirradiated control mice captopril biphasically modulated Lin− marrow progenitor cell cycling. After 2 days, captopril suppressed G0-G1 transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Linprogenitor cell cycling increased compared to untreated control mice. Conclusion These findings suggest that ACE inhibition affects hematopoietic recovery following radiation by modulating the hematopoietic progenitor cell cycle. The timing of captopril treatment relative to radiation exposure differentially affects the viability and repopulation capacity of spared hematopoietic stem cells and therefore can result in either radiation protection or radiation sensitization.

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Section: Discussionmentioning

confidence: 99%

Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation

Davis

Landauer²,

Mog³

et al. 2010

Experimental Hematology

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show abstract

“…The authors attributed this protection to increased free radical scavenging and reduced lipid per-oxidation/DNA damage. 47 In addition, captopril appears to decrease EPO transiently in nonirradiated controls and to increase EPO levels postirradiation if started prior to radiation exposure. When administered after a 7.5 G y whole body irradiation dose, captopril induced quiescence in hematopoietic stem cells, protecting them and leading to improved recovery postirradiation.…”

Section: Resultsmentioning

confidence: 95%

Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight

McLaughlin¹,

Donoviel²,

Jones³

2017

aerosp med hum perform

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Background In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile. Currently there are only three agents which have been clinically approved to be employed for radiation exposure, and these only for very narrow indications. This review identifies a number of agents currently approved by the U.S. Food and Drug Administration (FDA) which could warrant further investigation for use in astronauts. Specifically, we examine preclinical and clinical evidence for statins, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), metformin, calcium channel blockers, β adrenergic receptor blockers, fingolimod, N-acetylcysteine, and pentoxifylline as potential radiation countermeasures.

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“…54 Angiotensin-converting enzyme inhibitors (ACEIs) may reduce radiation-induced damage to the cardiopulmonary system by increasing free radical degradation and decreasing lipid peroxidation and DNA alterations. 55 However, their prophylactic use should be adequately evaluated in experimental studies. In the astronaut population, ACEIs and angiotensin II receptor blockers (ARBs) have caused major side effects such as renal perfusion and angioedema.…”

Section: Cardiovascular and Antihypertensive Drugsmentioning

confidence: 99%

Cosmic Radiations and the Cardiovascular System: A Narrative Review

Giacinto

Pelliccia

Minati

et al. 2022

Cardiology in Review

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In recent times, space flights receive continued interest. Humankind's next two goals are to return to the Moon and, a few years later, to land on the surface of Mars. Although technology will improve enough to enable long voyages, there are still some unresolved questions about the effects of the space environment on human health, including the effects of such long voyages on organs. Specifically, there is no information on the effects of radiation in space on the human cardiovascular system. To better understand the adaptation of the cardiovascular system to radiation exposure, the physical properties of radiation and the cellular and molecular mechanisms underlying tissue changes are essential. To this end, this article aims to provide an overview of the effects of radiation on the cardiovascular system by analyzing the physical properties of radiation and their relationship to cellular and molecular mechanisms and potential changes. Each type of radiation triggers different responses in the cardiovascular system. Radiation plays a relevant role in altering endothelial function and arterial wall stiffness by inducing vascular changes that accelerate atherosclerosis and affect endothelial adhesiveness. Clinical studies have shown that vascular changes due to radiation depend on the delayed manifestations of early radiation damage. To reduce the effects of radiation in space, some pharmacological treatments that seem to be able to counteract oxidative stress during flight are being used. At the same time, new shielding systems that can reduce or eliminate radiation exposure must be developed. Future studies should aim to replicate flights in the deep space environment to study in more detail the harmful effects of radiation on the whole cardiovascular system.

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Captopril protects mice bone marrow cells against genotoxicity induced by gamma irradiation

Cited by 11 publications

References 23 publications

Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation

Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation

Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight

Cosmic Radiations and the Cardiovascular System: A Narrative Review

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