Novel Indications for Commonly Used Medications as Radiation Protectants in Spaceflight

Abstract

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.

Ionizing Radiation induction of cholesterol biosynthesis in Lung tissue

“…Simvastatin and Lovastatin have been shown to reduce radiation induced inflammatory and pro-fibrotic markers without affecting DNA repair in normal tissues 39,40 . Thus, statin use poses many advantages as a mitigation agent by, in addition to reducing cholesterol synthesis, targeting other radiation-induced alterations in addition to reducing cholesterol synthesis 41 .…”

Clinical efficacy of acetylcysteine combined with tetrandrine tablets on patients with silicosis and its effect on exercise tolerance and pulmonary function

“…on neutrophil chemotaxis in bronchial mucosa of silicosis patients (10). Tetrandrine, as an alkaloid, plays a major role in analgesia, anti-inflammation, and can effectively improve pulmonary vascular smooth muscle spasm, thereby improving pulmonary microcirculation, thus reducing clinical features such as cough and chest tightness in patients (11,12).…”

“…Acetylcysteine, the main active component of acetylcysteine effervescent tablets, is widely used in the treatment of many respiratory diseases, such as bronchial asthma, chronic obstructive pulmonary disease because it can dissolve concentrated phlegm ( 9 ). In addition, it has been reported that acetylcysteine has antioxidant and inhibitory effects on neutrophil chemotaxis in bronchial mucosa of silicosis patients ( 10 ). Tetrandrine, as an alkaloid, plays a major role in analgesia, anti-inflammation, and can effectively improve pulmonary vascular smooth muscle spasm, thereby improving pulmonary microcirculation, thus reducing clinical features such as cough and chest tightness in patients ( 11 , 12 ).…”

Assessment of Radiosensitivity and Biomonitoring of Exposure to Space Radiation

“…Therefore, other protection measures such as onboard biodosimetry, or therapeutic measures, should also be considered, although their effectiveness in deep space is not yet established. Currently, several radioprotectors are available that can prevent and/ or reduce radiation-induced health effects by enhancing the body's natural capacity to repair cell damage caused by radiation or by preventing DNA damage to occur (McLaughlin et al 2017;Smith et al 2017). Another possible preventive measure could be to include the individual's radiation resistance to the induction of early and late radiation effects in the medical assessment of the mission crew applicants.…”