Effect of high oxygen pressure on the protective action of cystamine and 5-hydroxytryptamine in irradiated rats.

Abstract

BOTH the oxidized disulphide, cystamine (—S—S—) and its corresponding sulphydryl amine, cysteamine (—SH) are excellent radioprotective agents in vivo 1. If rats, protected by the latter reduced substance, respire pure oxygen under pressure (4–5 atmospheres absolute) at the time of irradiation, the protective action is completely reversed2,3 and this result also applies to cysteine. Our own findings have shown that this reversal also applies to the pharmacologically active amines, histamine and adrenalin, and largely to 5-hydroxytryptamine (vide infra). The lessening of the radioprotective action of these reducing agents by an increased oxygen pressure in tissue fluids may be due to the inactivation of additional —SH and reducing groups supplied to the body, or due to an increase in physical solution and diffusion of oxygen so provided, in overcoming the anoxaemia caused by either decreased oxygen-carrying capacity of haemoglobin (for example, with paraaminopropiophenone3), or by smooth muscle constriction in bronchioles or arterioles resulting from pharmacological action (for example, 5-hydroxytryptamine4). However, the protective disulphide, cystamine (—S—S—), is reduced to cysteamine (—SH), in vivo 5 and in vitro 6, and increased oxygen pressure in vivo may be expected to lessen its protective action, if the latter depends on the reduction of cystamine in tissues, to produce available —SH groups, or promote pharmacological activity, both of which tend to result in intracellular anoxia.