A Study of the Chlorpromazine Induced Decreased Liver Glutathione Reaction.

Abstract

Bartlett and Register ( 1) reported that administration of chlorpromazine to rats induced a lowering of liver non-protein sulfhydryl (NPSH) . The decreased liver NPSH reaction is also elicited by a number of nonspecific stressors( 2-4). Register and Bartlett ( 5 ) have shown that injection of epinephrine into rats produced the decreased liver NPSH reaction. Earlier work in these laboratories(6) has shown that in addition to epinephrine, administration of the psychotomimetic agents lysergic acid diethylamide, mescaline and serotonin produces a lowering of rat liver NPSH. The major portion of total NPSH in tissue is composed of reduced glutathione and changes in tissue concentrations of NPSH are due to changes in concentrations of reduced glutathione ( 7).This investigation concerns the mechanism through which chlorpromazine decreases liver glutathione.Methods. Determination of liver concentrations of glutathione was made by the amperometric titration procedure of Benesch and Benesch (8) employed in our laboratories (4,6, 9 and 10).One group of 10 female Holtzman rats ( 150-200 g) received intraperitoneal injections of 10 mg/kg of chlorpromazine while 2 other ~~ Mental Health. Hazleton Laboratories, Falls Church, Va. pharmacy, Pocatello.'groups received saline. Twenty-four hours after the first injections the chlorpromazine treated rats received a second injection of 10 mgJkg of chlorpromazine. The 2 remaining groups were administered 10 mg/kg of chlorpromazine and an equal volume of saline, respectively. The rats were sacrificed 4 hours after the final injection for liver glutathione determination. In a second experiment 6 rats were injected with 10 mg/kg of chlorpromazine while a second group received saline. The rats were sacrificed 8 hours after the injections and liver glutathione levels determined.Rats adrenalectomized 24 hours prior to the experiment were maintained at room temperature, received standard Wayne Lab Blox and 1% sodium chloride ad libitum. Twelve rats received 10 mgJkg of chlorpromazine and 10 received saline. Four hours after the injections the rats were sacrificed for liver glutathione determinations.Hypophysectomized rats$ were used' immediately upon receipt and required \no special treatment. Approximately 8 hours after surgery 6 of the rats received injections of 10 mgJkg of chlorpromazine and a second group of operated rats were subjected to bilateral hind leg rubber band tourniquet stress. The tourniquets were removed after 3% hours. The rats were sacrificed 4 hours after administration of chlorpromazine or application of the tourniquets.