The effects of hymenoxon on glucose metabolism in rat brain

Abstract

Hymenoxon is a toxic sesquiterpene lactone isolated from the range plant bitterweed (Hymenoxys odorata). Sheep, goats and cattle poisoned by ingestion of bitterweed have central nervous system (CNS) depression which, in time becomes severe and causes death. The lactone produces similar CNS depression and is toxic to sheep (intraperitoneal LD₅₀, 7mg/kg). The literature provides evidence that similar lactones of plant origin have growth inhibitory action against tumor systems. This action is attributed to the lactone reaction with essential sulfhydryl groups of phosphofructokinase causing inhibition of glucose metabolism. On the basis of this evidence and the CNS effects produced by bitterweed and hymenoxon, it was hypothesized that bitterweed is toxic to range animals because hymenoxon inhibits glucose metabolism in nervous tissue. Similar CNS depression has been reported in rats treated with hymenoxon. I found that one rat, under observation until it died 13 hr after intraperitoneal administration of 200 mg/kg of hymenoxon, had general depression. This rat became less reactive to external stimuli as time increased and was comatose at 10 hr. In order to establish the mode of action of hymenoxon, the effects of the bitterweed lactone on glucose metabolism in the brain was tested using the rat as the experimental animal. Neutral extracts from the brains of rats were analyzed spectrophotometrically for changes in glucose, glycolytic metabolite and sulfhydryl group concentrations in response to in vivo and in vitro exposure to hymenoxon..