[Effects of diispropyl 1, 3-dithiol-2-ylidene malonate (NKK-105) on the drug-metabolizing enzymes and fine structure of rat liver (author's transl)].
The mechanism of liver enlargement and anti-fatty liver effect of NKK-105 in the rat were investigated by the mesurement of drug-metabolizing enzyme activities and morphological changes in liver tissue detected using electron microscopy. A single administration of NKK-105(250, 500, 1000 mg/kg, p.o.) induced an apparent increase in liver weight. The elevation of aminopyrine demethylase activity and slight increase in microsomal cytochrome b5 and cytochrome P-450 content were seen with the administration of NKK-105. NKK-105 inhibited lipid peroxide formation in mitochondrial and microsomal fractions. Total lipid content of liver decreased at 12 hr after the administration of NKK-105. Lipid peroxide formation in mitochondrial and microsomal fractions was markedly inhibited by the addition of NKK-105 (1 X 10(-3)M), in vitro. Disarrangement of rough endoplasmic reticulum and increase in smooth endoplasmic reticulum were observed by the administration of NKK-105. The decrease in drug-metabolizing enzymes caused by CCl4 or ethionine was protected in the combination with NKK-105. NKK-105 markedly inhibited the elevation of lipid peroxide formation caused by CCl4 or ethionine. Similar effects on lipid peroxide formation were also obtained in vitro. These results suggest that the enlargement induced by NKK-105 indicates a functional not a toxic response. The inhibition of lipid peroxide formation in mitochondrial and microsomal fractions may thus play an important role in the mechanism of anti-fatty liver effect of NKK-105 on the CCl4 or ethionine-induced fatty liver.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005001:Ethionine / Q000633:toxicity; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology*
D008054:Lipid Peroxides; D008314:Malonates; D013876:Thiophenes; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D000633:Aminopyrine N-Demethylase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate; D005001:Ethionine; D010634:Phenobarbital