実験的四塩化炭素中毒におけるpyruvate代謝の研究

第2編 四塩化炭素中毒の回復期及び薬物負荷時の肝組織及び血液中pyruvateの変動

抄録

The concentrations of pyruvate and related compounds in the liver and blood in the recovery 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 recovery 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.
(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 -ß aminoethyl) disulfide), a precursor of coenzyme A, to carbontetrachloride-intoxicated rats arrested the progression 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 administration. 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 carbontetrachloride depends largely on DPN contents.