Salicylate and Liver Glutathione

Abstract

The effects of sodium salicylate, benzoate, gentisate, m-and p-hydroxybenzoates, antipyrine, and 2: 4-dinitrophenol on the reduced glutathione concentration of rat liver were determined. An increase in concentration in the male, but not in the female, rats was found after salicylate, benzoate and gentisate; after antipyrine, a comparable increase occurred in the females only. There is a relation, in these compounds, between capacity to increase the concentration of reduced glutathione in the rat liver in one sex and therapeutic activity in rheumatic fever.In continuation of a search for pharmacological actions of salicylate which are correlated with its therapeutic properties, the effect of salicylate on the reduced glutathione concentration of liver was examined. A two-fold increase in the reduced glutathione concentration of rat liver after administration of sodium salicylate has been reported by Lutwak-Mann (1942). The present results do not confirm this finding: a moderate increase in the reduced glutathione concentration of rat liver was induced by salicylate, but in the male sex only.An attempt has been made to evaluate this finding, by comparing the activity of salicylate on rat liver glutathione with that of a variety of other compounds. In addition to salicylate, the following were studied: other antirheumatic drugs of the same series (benzoate and gentisate), and of a different series (antipyrine); m-and p-hydroxybenzoates, which are therapeutically inert isomers of salicylate, and 2:4-dinitrophenol, which, like salicylate, is a peripheral metabolic stimulant.In the first experiments, an interval between administration of the drug and termination of the experiment was arbitrarily selected as adequate and convenient for salicylate. This interval was unlikely to be suitable for the rapidly excreted compounds such as benzoate. Rather than find the optimal interval for each compound, a second series of observations was made, in which two doses were given of each of the compounds which in single doses of 200 mg/ 100 g body weight were tolerated without noticeable effect. Salicylate was included for comparative purposes.A relation was then found, within the present group of compounds, between therapeutic activity in rheumatic fever and capacity to increase rat liver glutathione concentration in one sex.

Gentisic Acid, a Quinonoid Aspirin Metabolite in Cancer Prevention and Treatment. New Horizons in Management of Brain Tumors and Systemic Cancers

“…In the future, it would be logical to evaluate intratumoral glutathione levels with GA exposure in future studies. In the intact organism, treatment of rats even with huge doses of GA (1 g/kg; corresponding to 70 g for an average human subject) did not reduce liver glutathione with single exposure, even slightly augments it with double exposure [94]. Hence, there would be unique opportunity that GA may selectively increase chemoradiotherapy toxicity in tumors while sparing benign tissues.…”