The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 76, 421-435, Copyright, 1942, by The Rockefeller Institute for Medical Research New York

ARTICLE

LIVER INJURY, LIVER PROTECTION, AND SULFUR METABOLISM : METHIONINE PROTECTS AGAINST CHLOROFORM LIVER INJURY EVEN WHEN GIVEN AFTER ANESTHESIA



L. L. Miller Ph.D.1 and G. H. Whipple M.D.1

1 From the Department of Pathology of The University of Rochester School of Medicine and Dentistry, Rochester, New York

Protein-depleted dogs are very susceptible to injurious agents—in particular, chloroform. Methionine given shortly before chloroform anesthesia will give complete protection against chloroform. Methionine (or cysteine plus choline) given 3 or 4 hours after chloroform anesthesia will give significant protection against the liver injury of chloroform anesthesia. Methionine given more than 4 hours after chloroform anesthesia gives no protection against liver injury. Choline alone given before chloroform gives no protection against liver injury.

The protein-depleted dogs have livers which are deficient in both nitrogen and sulfur, but sulfur is depleted more than is the nitrogen. The N/S ratio therefore rises. Methionine or cystine feeding promptly makes up this liver sulfur deficit. Viable liver cells are necessary for this uptake of sulfur.

Livers of fetuses in utero or of newborn pups tolerate a chloroform anesthesia which will cause fatal liver injury in adults. The nitrogen and sulfur values of these fetus or pup livers are within the high normal values for adults. Blood-forming cells are present in the fetus or pup livers during this period. When these blood islands are eliminated during the 3rd or 4th week of life, the liver then becomes normally susceptible to chloroform liver injury.

Methionine or methionine-rich protein digests (e.g. casein) or various proteins by mouth or by vein should prove useful to protect the liver against certain types of injury and to aid in organ repair.

 Submitted on July 31, 1942


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