8-Azaguanine, 3, 3' -4, 4' -tetrahydroxy-chalcone and purine in experimental shock in the rat

¹ Department of Pathology, New York University-Bellevue Medical Center, New York City

Two substances, 8-azaguanine (8AG) and 3, 3' -4, 4' -tetrahydroxy-chalcone (THC), believed to be nonoxidized in vivo inhibitors of xanthine oxidase in the rat, were used in an attempt to depress iron-release mechanisms during shock. Purine, a substrate of xanthine oxidase, was administered during shock as a means of stimulating these same mechanisms. No protection was obtained with 8AG and subsequent tests revealed that 8AG failed to depress the release of iron and uric acid both in shocked and untreated rats. The data point, instead, to inhibition of uricase by 8AG in the intact rat and not to inhibition of xanthine oxidase activity. Despite occasional depression of xanthine oxidase activity, THC exacerbated the course of traumatic shock in rats, possibly as a result of interference with pressor amine mechanisms. Purine loads were administered to normal rats and to rats primed with thorotrast. Although purine is known to elevate plasma iron in other species, rats treated with this metabolite were not unusually susceptible to lethal traumatic injury.