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8 1) Sherlock, S., & Walshe, V.: Lancet 251, 482, ) Caravati, C. M.: Southern M. J. 37, 251, , , , , , 1966.

9 9) Kalk, H.: Zirrhose und Narbenleber, Ferdinand Euke Verlag, Stuttart, ) Doljanski, F.: Intern. Rev. Cytol. 10, 217, ) Harkness, R. D.: Brit. Med. Bull. 13, 87, ) Abercrombie, M.: Symposia Soc. Exptl. Biol. 11, 235, ) Weinbren, K. Gastroenterol. 37, 657, ) Brauer, R. W.: Physiol. Revs. 43, 115, ) Mann. F. C.: J. Mt. Sinai. Hosp. 11, 65, ) Wilson, J. W.: Ann. Rev. Physiol. 13, 133, ) Mann, F. C.: Ann. Rev. Physiol. 15, 473, ) Davidson, J. N.: Brit. Med. Bull. 13, 71, ) Paschkis, K. E.: Canser Res. 18, 981, ) Novihoff, A. B.: Am. J. Med. 29, 102, ) Bollman, J. L.: Ann. Rev. Physiol. 23, 183, ) Bucher, N. L. R.: Intern. Rev. Cytol. 15, 245, ) Schneider, W. C.: J. Biol. Chem. 176, 259, ) Shimizu, T.: J. Biochem. 38, 99, ) Barker, S. B. & Summerson, W. H.: J. Biol. Chem. 138, 535, ) Somogyi, M. & Nelson, J. F.: J. Biol. Chem. 195, 19, ) Fishback, F. C.: A. M. A. Arch. Pathol. 7, 954, ) Bollman, J. L.: Ergeb. Physiol. U. Exptl. Pharmahol. 38, 445, ) Glinos, A. D.: In "The chemical Basis of De velopment" (Eds. McElroy, W. D. & Glass, B.) p. 813, Johns Hopkins press, Baltimore, Mary land ) Brauer, R. W.: In Liver Function (Ed. Brauer, R. W.), Publ. No. 4. Am. Inst. Biol. Sci., Washington, D. C ) Bernhard, W. & Rouiller, C.: J. Biophys. Bio chem. Cytol. 2, (Suppl.) 73, ) Bernhard, W.: Exptl. Cell. Res. Suppl. 9, 17, ) Vagra, F., Meres, Gy. & Molnar, Z.: Acta. Physiol. Acad. Sci. Hung. 29, 69, ) Quinn, P. S. & Higginson, J.: Am. J. Pathol, 47, 353, ) Gear, A. R. L.: Biochem. J. 97, 532, ) Sanchez, E., Soberon, G., Palacios, O. Lee, E. & Kuri, M.: J. Biol. Chem. 236, 1607, ) Soberon, G. & Sanchez, E.: J. Biol. Chem. 236, 1602, ) Pollak, J. K.: Exptl. Cell. Res 19, 156, ) Smith, H. M.: Proc. Soc. Exptl. Biol. Med. 109, 182, ) Fritzson, P.: Biochem. Biophys. Acta. 91, 374, ) Sakamoto, K.: Jap. Achr. Intern. Med. 12, 603, ) Schmidt, A. J.: J. Exptl. Zool. 145, 43, ) Johnson, E. A. & Singer, M.: Proc. Soc. Exptl. Biol. Med. 117, 27, ) Schmidt, A. J. & Weidman, T.: J. Exptl. Zool. 155, 303, ) Wolfe, H. J. & Cohen, R. B.: Develop. Biol. 8, 48, ) Isselbacher, K. J. & Jones, W. A.: Gastroentero logy. 46, 424, ) Gear, A. R. L.: Biochem. J. 95, 118, ) Allard, C., De Lamiraude, G. & Cantero, A.: Cancer Res. 12, 580, ) Morison, G. R., Brock, F. E., Karl, I. E. & Shank, R. E.: Arch. Biochem. Biophys. 111, 448, ) Needham, A. E.: Fumdamental aspect of normal and malignant growth. (Ed. Nowinski, W. W.), p. 588, Elsevier Publ. Co. Amsterdam ) Oreshnikova, N. A., Novikova, M. Q. & Zhdanov, G. L.: Vop. Med. Khim. 11, 67, ) Kono, H.: Acta, Med. Okayama, 18, 15,1964.

10 60) Levintow, L. & Novelli, G. D.: J. Biol. Chem. 207, 761, ) Brown, G. M.: J. Biol. Chem. 234, 370, ) Piccinelli, O.: Farmaco (pavia) Ed. Sci. 12, 799, ) Garattini, S.: Soc. Lombarda. Sci. Med. e Biol. Riunione in Milano, 7 Maggio ) Annoni, G. & Leone, M.: Minerva Medica, 46, 756, ) Farber, E.: Arch. Path. 67, 1, ) Villa-Trevino, S, Shull, K. H. & Farber, E.: J. Biol. Chem. 238, 1757, ) Farber, E., Sbull, K.H. & Villa-Trevino, S.: Nature 203, 34, ) Soberon, G.: Arch. Biochem. Biophys. 103, 331, ) Cohen, G. & Hochstein, P.: Biochemistry 2, 1420, ) Strauss, E. & Hiller. J.: Vern. Dtsch. Gesṣ Inn. Med. Wschr. 96, 227, ) Kleinsorge, H. & Schuchordt, H.: Munch. Med. Wschr. 96, 227, ) Gallagher, C. M. & Rees, K. R.: Nature 187, 148, ) Tholen, H., Bigler, F., Heusler, A. & Staub, H.: Dtsch. Med. Wschr. 87, 2488, Studies on Pyruvate Metabolism in Carbontetrachlorideintoxicated Rats Pyruvate Concentrations in the Liver and Blood in the Recovery from Carbontetrachloride Intoxication and the Effect of Pantethine, ATP and DPN By Masao NAKASHIMA The First Department of Internal Medicine Okayama University Medical School (Director: K. Kosaka) The concentrations of pyruvate and related compounds in the liver and blood in the reco very of carbontetrachloride intoxication of rats were measured and the effects of pantethine, ATP and DPN administrations were studied. (1) In the recovery stage from acute carbontetrachloride intoxication, the first and fourth weeks after single subcutaneous administration of carbontetrachloride, and in the reco very stage from chronic carbontetrachloride intoxication, the second and fourth weeks after subcutaneous injection of carbontetrachloride twice a week for four weeks, serum transaminase activities (S GOT and S GPT) returned normal and the histological changes of liver (heamatoxylin-eosin staining) were also normal except for slight irregular cellular ridges and cytoplasmic basophilia.

11 (2) Decreased pyruvate oxidation in the rat liver mitochondria was still present even though no significant histological changes could be demonstrated microscopically. This might mean that the function of mitochondrial enzymes would not be restored in a shorter time. In the first and fourth weeks of recovery from the acute intoxication, increases of the lactate/pyruvate ratio of the liver were observed. The pyruvate level in the liver did not show any significant change in the recovery from acute and chronic intoxications. (3) Intraperitoneal administration of pantethine (Bis (N-pantotenyl disul fide), a precursor of coenzyme A, to carbontetrachloride-intoxicated rats arrested the progres sion of fibrosis and the formation of pseudoacinus of the liver. The diffuse fatty infiltration of the liver, however, was not prevented by pantethine. The fact that no improvement of the pyruvate-oxidizing activity (QO2) of liver mitochondria, a decrease of pyruvate level and an increase of cholesterol in the blood were observed with pantethine seems to suggest that the diffuse fatty infiltration of the liver by pantethine might be resulting from decreases of hepatic ATP level and -SH enzyme activities, which would be caused by pantethine administra tion. Pantethine improved other routine liver fanction tests except for Zinc sulfate test. (4) Simultaneous administration of pantethine and ATP reduced the extent of diffuse fatty infiltration of the liver. The blood sugar decreased by pantethine and ATP more than by pantethine alone probably due to an insulin like activity of ATP. The blood cholesterol increased, and QO2 and other routine liver function tests were improved more by pantethine and ATP than by pantethine alone. (5) Intraperitoneal administration of DPN to carbontetrachloride-intoxicated rats resulted in marked improvements in liver histology, QO2, lactate/pyruvate ratio of the liver and the other liver function tests. These results seem to suggest that the progression of the liver injury by carbontetra chloride depends largely on DPN contents.

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