BIOCHEMICAL ALTERATIONS OF LIVER FUNCTION BY THE HALOGENATED HYDROCARBONS. I. IN VITRO AND IN VIVO CHANGES AND THEIR MODIFICATION BY ETHYLENEDIAMINE TETRAACETATE

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor

In vitro treatment of liver mitochondria with carbon tetrachloride results in a depression of DPN-linked dehydrogenase activity. The addition of DPN partially restores oxidation. Oxidative phosphorylation is inhibited, but this effect is probably the result of a magnesium ATP-ase activation. The oxidation of choline is enhanced. These changes can be blocked by the concomitant addition of Versene.

The same general pattern in oxidation and phosphorylation is observed with the oral administration of carbon tetrachloride. In addition changes are seen in tissue sodium and potassium concentrations and in serum glutamic-oxaloacetic transaminase activity. All effects are modified by Versene administered simultaneously.

Choline administration failed to protect against the metabolic changes induced by carbon tetrachloride.

There did not appear to be any correlation between metabolic alterations and histologic findings.

The possible mechanisms by which Versene protects are discussed.