E.s.r. study of decay of the nitroxyl free radical TAN in whole rats and rat-tissue homogenates

The loss of the radical property of TAN (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) in the blood of anaesthetized rats has been studied by e.s.r.. Some physiological techniques, such as ligating the portal vein and the abdominal aorta, and also sympathetic blockade, were used to elucidate possible mechanisms of the TAN decay process. Similar decay curves were obtained with rats at normal (370C) and lowered (27 to 280C) body temperatures, indicating the involvement of processes other than enzymic in the in vivo decay of TAN. The fast decay could not be explained by reaction of TAN with other components of blood, since in vitro TAN in blood lost its radical property very slowly. Evidence was obtained for the conversion of TAN to TMPN in the kidney of rats anaesthetized with ether, but not with Nembutal. The greater half-value time recorded in rats with interrupted portal circulation may indicate that the liver is an essential factor in the degradation of TAN. A temperature-dependent TAN decay was observed with in vitro mixtures with homogenates of organs and the decay was faster with homogenates of kidney and liver than brain, lungs and heart, suggesting that enzymic processes do control the in vitro decomposition of TAN. Consideration is given to implications of these results for the potential applications of TAN as a radiosensitizer. (U.K.)