CARBON TETRACHLORIDE HEPATOTOXICITY: THE DIRECT ACTION OF CCl₄ ON THE LIVER

¹ Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

Carbon tetrachloride, when injected directly into the portal venous cannula of an isolated perfused rat liver, inhibited the net outward transport of hepatic triglycerides. This effect of CCl₄ appears to be reversible and dose-dependent. The hypothesis that CCl₄ poisoning exerts its hepatotoxic action via adrenalmedullary discharge of catecholamines and stimulation of sympathetic autonomic nerves to the liver appears to be untenable since 1) the isolated perfused liver cannot be affected in such a manner, 2) adrenergic blocking agents and reserpine do not block the inhibitory effect of CCl₄ on triglyceride release, and 3) both epinephrine and norepinephrine inhibit fatty acid uptake, decrease hepatic blood flow, and stimulate glucose release by the liver-actions which are not elicited by CCl₄. These observations are discussed with reference to current knowledge concerning the mechanism of production of fatty liver and hepatic necrosis in CCl₄ intoxication.