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PROTECTIVE ACTION OF VITAMIN C AGAINST EXPERIMENTAL HEPATIC DAMAGE

PROTECTIVE ACTION OF VITAMIN C AGAINST EXPERIMENTAL HEPATIC DAMAGE Abstract An associate and I1 previously found that if a hepatoxin, carbon tetrachloride, were given to dogs they could be made to excrete all instead of about half of a given dose of the sympathomimetic amine amphetamine. More recently I showed that if dogs were put on a maintenance dose of the amine, saturating the animals with vitamin C (ascorbic acid) would reduce the excretion of amphetamine to about one third of the amount normally excreted.2 This together with the in vitro deamination of the amine demonstrated the role of ascorbic acid in the detoxication of these compounds. However, to our surprise, if dogs saturated with vitamin C were given carbon tetrachloride orally, the excretion of amphetamine did not rise above normal. These observations suggested that ascorbic acid might protect the animals against the toxic action of carbon tetrachloride on the liver. It was deemed more suitable to turn References 1. Beyer, K. H., and Skinner, J. T.: The Detoxication and Excretion of Beta Phenylisopropylamine (Benzedrine) , J. Pharmacol. & Exper. Therap. 68:419 ( (April) ) 1940. 2. Beyer, K. H.: The Action of Vitamin C and Phenol Oxidase in the Inactivation of Beta Phenylisopropylamine , J. Pharmacol. & Exper. Therap. 71:394 ( (April) ) 1941. 3. The composition of the diet was as follows: protein, 15.35 per cent; fat, 2.38 per cent; carbohydrates, 64.61 per cent (including 16.86 per cent fiber); calcium carbonate; phosphorus; sodium chloride; potassium iodide; magnesium sulfate, and per pound (0.5 Kg.) approximately 5,000 international units of vitamin A, approximately 400 international units of vitamin B1, approximately 3,000 micrograms of riboflavin (vitamin B2) and negligible vitamin C. 4. Ecker, E. E., and Pillemer, L.: Vitamin C Requirement of the Guinea Pig , Proc. Soc. Exper. Biol. & Med. 44:262 ( (May) ) 1940. 5. Wells, H. G.: The Pathological Anatomy of Hydrazine Poisoning , J. Exper. Med. 10:457 ( (July) ) 1908. 6. Underhill, F. P., and Kleiner, J. S.: The Influence of Hydrazine upon Intermediary Metabolism in the Dog , J. Biol. Chem. 4:165 ( (Feb.) ) 1908. 7. Spellberg, M. A., and Keeton, R. W.: Production of Fatty Livers in Guinea Pigs with Scorbutogenic Diets , Proc. Soc. Exper. Biol. & Med. 41:570 ( (June) ) 1939. 8. Beddard, A. P.: A Suggestion for Treatment in Delayed Chloroform Poisoning , Lancet 1:782 ( (March 14) ) 1908. 9. Rosenfeld, G.: Fat Synthesis: Part II , Ergebn. d. Physiol. 2:50, 1903. 10. Miller, L. L., and Whipple, G. H.: Chloroform Liver Injury Increases as Protein Stores Decrease: Studies in Nitrogen Metabolism in These Dogs , Am. J. M. Sc. 199: 204 ( (Feb.) ) 1940. 11. Messinger, W. J., and Hawkins, W. B.: Arsphenamine Liver Injury Modified by Diet: Protein and Carbohydrate Protective, but Fat Injurious , Am. J. M. Sc. 199:216 ( (Feb.) ) 1940. 12. Ravdin, I. S.: The Protection of the Liver from Injury , Surgery 8:204 ( (Aug.) ) 1940. 13. Miwa, A.: Golgi's Apparatus and Vitamin C: Experimental Studies , Orient. J. Dis. Infants 26:3 ( (July) ) 1939. 14. Murakami, O.: The Influence of Ascorbic Acid upon the Liver Function and the Mutual Relation Between Vitamins B and C: I. Influence of Ascorbic Acid upon the Pigment Excreting Function of the Liver , Jap. J. Gastroenterol. 11:1 ( (July) ) 1939. 15. Abderhalden, E., and Bergell, P.: Concerning the Elimination of Monoaminoacids in the Urine of Dogs Following Phosphorus Poisoning , Ztschr. f. physiol. Chem. 39:464, 1903. 16. Romanyuk, N. M.: Cathepsin Activity in the Brain and Muscles During C Avitaminosis , Biochem. J. (Ukraine) 14:354, 1940. 17. Levine, S. Z.; Marples, E., and Gordon, H. H.: Defect in the Metabolism of Aromatic Amino Acids in Premature Infants: The Role of Vitamin C , Science 90:620 ( (Dec. 29) ) 1939. 18. Sealock, R. R., and Silberstein, H. E.: The Excretion of Homogentisic Acid and Other Tyrosine Metabolites by the Vitamin C Deficient Guinea Pig , J. Biol. Chem. 135:251 ( (Aug.) ) 1940. 19. Saikowsky: Concerning the Fatty Metamorphosis of the Organs Following the Internal Use of Arsenic, Antimony and Phosphorus , Virchows Arch. f. path. Anat. 34:73, 1865. 20. Ratsimamanga, A. R.: The Influence of Ascorbic Acid on the Behavior of the Organism at Rest , Travail humain 1:303, 1939. 21. Watanabe, I.: Effect of Various Vitamins on Glycogen Content of Experimentally Damaged Liver , Tohoku J. Exper. Med. 35:65 ( (Jan.) ) 1939. 22. Morelli, A., and d'Ambrosio, L.: Ascorbic Acid and Liver Glycogen , Arch. di sc. biol. 24:351 ( (Aug.) ) 1938. 23. Terada, K.: Effect of Vitamin C and Related Substances upon Glycogen Metabolism , Tohoku J. Exper. Med. 36:180 ( (July) ) 1939.Crossref 24. Hjorth, P.: The Influence of Vitamin C on Carbohydrate Metabolism , Acta med. Scandinav. 105:67, 1940.Crossref 25. Dienst, C.: Action of Vitamins B and C in Diabetes , Deutsche med. Wchnschr. 65: 710 ( (May 5) ) 1939.Crossref 26. Fan, C., and Woo, T. T.: Effect of Vitamin C on Creatine and Creatinine Metabolism , Proc. Soc. Exper. Biol. & Med. 45:90 ( (Oct.) ) 1940. 27. Vasile, B., and Pecorella, F.: The Influence of Vitamins on the Metabolism of Creatin. Substances in Childhood: I. The Effect of Vitamin C , Pediatria 47:130 ( (Feb.) ) 1939. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

PROTECTIVE ACTION OF VITAMIN C AGAINST EXPERIMENTAL HEPATIC DAMAGE

Archives of Internal Medicine , Volume 71 (3) – Mar 1, 1943

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American Medical Association
Copyright
Copyright © 1943 American Medical Association. All Rights Reserved.
ISSN
0730-188X
DOI
10.1001/archinte.1943.00210030016002
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Abstract

Abstract An associate and I1 previously found that if a hepatoxin, carbon tetrachloride, were given to dogs they could be made to excrete all instead of about half of a given dose of the sympathomimetic amine amphetamine. More recently I showed that if dogs were put on a maintenance dose of the amine, saturating the animals with vitamin C (ascorbic acid) would reduce the excretion of amphetamine to about one third of the amount normally excreted.2 This together with the in vitro deamination of the amine demonstrated the role of ascorbic acid in the detoxication of these compounds. However, to our surprise, if dogs saturated with vitamin C were given carbon tetrachloride orally, the excretion of amphetamine did not rise above normal. These observations suggested that ascorbic acid might protect the animals against the toxic action of carbon tetrachloride on the liver. It was deemed more suitable to turn References 1. Beyer, K. H., and Skinner, J. T.: The Detoxication and Excretion of Beta Phenylisopropylamine (Benzedrine) , J. Pharmacol. & Exper. Therap. 68:419 ( (April) ) 1940. 2. Beyer, K. H.: The Action of Vitamin C and Phenol Oxidase in the Inactivation of Beta Phenylisopropylamine , J. Pharmacol. & Exper. Therap. 71:394 ( (April) ) 1941. 3. The composition of the diet was as follows: protein, 15.35 per cent; fat, 2.38 per cent; carbohydrates, 64.61 per cent (including 16.86 per cent fiber); calcium carbonate; phosphorus; sodium chloride; potassium iodide; magnesium sulfate, and per pound (0.5 Kg.) approximately 5,000 international units of vitamin A, approximately 400 international units of vitamin B1, approximately 3,000 micrograms of riboflavin (vitamin B2) and negligible vitamin C. 4. Ecker, E. E., and Pillemer, L.: Vitamin C Requirement of the Guinea Pig , Proc. Soc. Exper. Biol. & Med. 44:262 ( (May) ) 1940. 5. Wells, H. G.: The Pathological Anatomy of Hydrazine Poisoning , J. Exper. Med. 10:457 ( (July) ) 1908. 6. Underhill, F. P., and Kleiner, J. S.: The Influence of Hydrazine upon Intermediary Metabolism in the Dog , J. Biol. Chem. 4:165 ( (Feb.) ) 1908. 7. Spellberg, M. A., and Keeton, R. W.: Production of Fatty Livers in Guinea Pigs with Scorbutogenic Diets , Proc. Soc. Exper. Biol. & Med. 41:570 ( (June) ) 1939. 8. Beddard, A. P.: A Suggestion for Treatment in Delayed Chloroform Poisoning , Lancet 1:782 ( (March 14) ) 1908. 9. Rosenfeld, G.: Fat Synthesis: Part II , Ergebn. d. Physiol. 2:50, 1903. 10. Miller, L. L., and Whipple, G. H.: Chloroform Liver Injury Increases as Protein Stores Decrease: Studies in Nitrogen Metabolism in These Dogs , Am. J. M. Sc. 199: 204 ( (Feb.) ) 1940. 11. Messinger, W. J., and Hawkins, W. B.: Arsphenamine Liver Injury Modified by Diet: Protein and Carbohydrate Protective, but Fat Injurious , Am. J. M. Sc. 199:216 ( (Feb.) ) 1940. 12. Ravdin, I. S.: The Protection of the Liver from Injury , Surgery 8:204 ( (Aug.) ) 1940. 13. Miwa, A.: Golgi's Apparatus and Vitamin C: Experimental Studies , Orient. J. Dis. Infants 26:3 ( (July) ) 1939. 14. Murakami, O.: The Influence of Ascorbic Acid upon the Liver Function and the Mutual Relation Between Vitamins B and C: I. Influence of Ascorbic Acid upon the Pigment Excreting Function of the Liver , Jap. J. Gastroenterol. 11:1 ( (July) ) 1939. 15. Abderhalden, E., and Bergell, P.: Concerning the Elimination of Monoaminoacids in the Urine of Dogs Following Phosphorus Poisoning , Ztschr. f. physiol. Chem. 39:464, 1903. 16. Romanyuk, N. M.: Cathepsin Activity in the Brain and Muscles During C Avitaminosis , Biochem. J. (Ukraine) 14:354, 1940. 17. Levine, S. Z.; Marples, E., and Gordon, H. H.: Defect in the Metabolism of Aromatic Amino Acids in Premature Infants: The Role of Vitamin C , Science 90:620 ( (Dec. 29) ) 1939. 18. Sealock, R. R., and Silberstein, H. E.: The Excretion of Homogentisic Acid and Other Tyrosine Metabolites by the Vitamin C Deficient Guinea Pig , J. Biol. Chem. 135:251 ( (Aug.) ) 1940. 19. Saikowsky: Concerning the Fatty Metamorphosis of the Organs Following the Internal Use of Arsenic, Antimony and Phosphorus , Virchows Arch. f. path. Anat. 34:73, 1865. 20. Ratsimamanga, A. R.: The Influence of Ascorbic Acid on the Behavior of the Organism at Rest , Travail humain 1:303, 1939. 21. Watanabe, I.: Effect of Various Vitamins on Glycogen Content of Experimentally Damaged Liver , Tohoku J. Exper. Med. 35:65 ( (Jan.) ) 1939. 22. Morelli, A., and d'Ambrosio, L.: Ascorbic Acid and Liver Glycogen , Arch. di sc. biol. 24:351 ( (Aug.) ) 1938. 23. Terada, K.: Effect of Vitamin C and Related Substances upon Glycogen Metabolism , Tohoku J. Exper. Med. 36:180 ( (July) ) 1939.Crossref 24. Hjorth, P.: The Influence of Vitamin C on Carbohydrate Metabolism , Acta med. Scandinav. 105:67, 1940.Crossref 25. Dienst, C.: Action of Vitamins B and C in Diabetes , Deutsche med. Wchnschr. 65: 710 ( (May 5) ) 1939.Crossref 26. Fan, C., and Woo, T. T.: Effect of Vitamin C on Creatine and Creatinine Metabolism , Proc. Soc. Exper. Biol. & Med. 45:90 ( (Oct.) ) 1940. 27. Vasile, B., and Pecorella, F.: The Influence of Vitamins on the Metabolism of Creatin. Substances in Childhood: I. The Effect of Vitamin C , Pediatria 47:130 ( (Feb.) ) 1939.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Mar 1, 1943

References