PHARMACOLOGICAL STUDIES OF DIISOPROPYL 1, 3-DITHIOL-2-YLIDENE MALONATE (NKK-105)

REPORT 4; EFFECTS OF NKK-105 ON CCl₄-INDUCED FATTY LIVER IN RATS

Abstract

We investigated the effects of combined administration or after treatment of NKK-105 and its related compounds on the CCl₄-induced fatty liver in the rats, and obtained the following results.
1) The liver per body weight (L/B) ratio increased by the administration of CCl₄ (0.5ml/kg, s. c. daily for 4 days) .
An increase of L/B ratio by CCl₄ inhibited by the administration of NKK-105 and its related compounds with a dose of 10-50 mg/kg, p, o.. But NKK-105 and its related compounds 250 mg/kg, p. o. administered group showed an increase of L/B ratio more than CCl₄ administered group.
2) CCl₄ administered group showed a decrease in protein of liver and serum.
NKK-105 and its related compounds inhibited the decrease of protein by the administration of CCl₄, especially in NKK-150 250 mg/kg, p. o. administered group and it was showed an increase of protein more than control group.
3) The liver lipids of CCl₄-induced fatty liver showed a significantly increase in total lipids (TL), total cholesterols (TC) and triglyceride (TG) and a slightly decrease in total phospholipids (PL) .
NKK-105 and its related compounds inhibited the increase of TL, TC and TG and decrease of PL by the administration of CCl₄. NKK-105 250 mg/kg, p. o. administered group showed an increase of PL more than control group.
4) The serum lipids of CCl₄-induced fatty liver showed a decrease of TL, TC, TG and PL.
NKK-105 and its related compounds inhibited the decrease of serum lipids by the administration of CCl₄. NKK-105 250 mg/kg, p. o. administered group showed an increase of over control group.
5) The rise of serum transaminase was observed by the administration of CCl₄.
This transaminase rising action of CCl₄ was inhibited by the administration of NKK-105 and its related compounds.
6) Histologic examination of CCl₄-induced fatty liver showed a centrilobular fatty degeneration, necrosis and loss of nucleus.
NKK-105 and its related compounds showed an inhibitory effect of these histological response to CCl₄ administration, especially in 250 mg/kg, p. o. of NKK-105 markedly.