Radioprotective Effects of Reserpine and its N-oxide

Abstract

CERTAIN amine oxides exert a protective effect against radiation injury^1,2. Reserpine has also been shown to have this action³. This suggested a comparison between reserpine and its N-oxide. Groups of 20 CF–1 mice were administered various doses of the two compounds 24 hr. before X-irradiation with 600 r. (Table 1). Radiation conditions were the same as described previously¹. Both compounds produced typical reserpine effects, sedation and ptosis, but the N-oxide was less active per dose. All three doses of reserpine N-oxide significantly increased the ST₅₀ day, whereas only one dose of reserpine had this effect (Table 1). On the basis of total survival it requires twice as much reserpine as its N-oxide to decrease mortality by 25 per cent, and neither compound is as effective as quinoxaline di-N-oxide¹ or anhydroerythromycin N-oxide². Mechanisms of action are probably different, since the reserpine compounds exert no antibiotic effects. However, they have the proper chemical structures postulated for removing oxidizing radicals². Protection might be partially the result of the release of known protective compounds, adrenaline and 5-hydroxytryptamine⁵. The release of catecholamines and 5-hydroxytryptamine is essentially complete 16 hr. after reserpine administration, and the binding sites, as well as the plasma content, do not begin to contain appreciable amounts of these amines for at least 4 days^6–9. Metabolism and excretion are also going on at this time, and in all probability the amount of such amines available for exerting a protective effect is below that necessary for such an action. On the other hand, reserpine has been found in body tissues for at least 48 hr. following a single dose¹⁰. Most of the reserpine was found in the tissue cells where, in the present radiation experiment, it could act as a protecting compound. The fact that reserpine and its N-oxide exert only a slight protective effect against lethal X-irradiation points out the need for continuing the search for compounds having low toxicity and greater protective effects at the cellular level.