Greatine Synthesis in the Perfused Liver of Normal and X-irradiated Rats

Abstract

One of the metabolic disorders observed in animals after exposure to ionizing radiation is an intense creatinuria ( 1,2,3,4). Recent studies indicate that the depressed capacity of the skeletal muscle to utilize creatine is responsible for the creatinuria observed after irradiation(5,6). On the basis of in vitro studies with liver homogenates it has also been suggested that the synthesis of creatine from glycocyamine is increased after x-irradiation ( 7).However, previous experiments carried out in this laboratory on in vivo synthesis of creatine from glycine-1-C14 in rats exposed to xirradiation( 2 ) do not support the hypothesis of an increased creatine synthesis. To determine whether creatine synthesis is increased after exposure to radiation, the rate of creatine synthesis from glycocyamine-2-CI4 in the isolated perfused liver of normal and x-irradiated rats has been studied and is reported here.Methods. Four rats of Sprague-Dawley strain were exposed to 650 r of x-rays(4) and starved thereafter for 18 hours. At this time, a significant elevation of the creatine levels of blood and urine was observed. Four other rats of the same strain, also starved for 18 hours, served as controls.The liver was removed from each rat and perfused with whole heparinized blood diluted with one-third volume of Ringer's solution containing 250 mg of glucose and 4 pc of glycocyamine-2-CI4 (0.185 mg) (purchased from the California Biochemical Corp.) . Blood donors were non-irradiated adult Sprague-Dawley rats fasted 18 to 20 hours before bleeding. Details of the perfusion technic and apparatus have been previously described ( 8,9).