Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol-2-ylidene)- 2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on active oxygen production.
The effects of KF-14363 on active oxygen production and membrane stabilization were studied. KF-14363 did not affect hypotonic hemolysis (10% and 70%) and did not inhibit lipid peroxide production induced by t-butyl hydroperoxide at concentrations of less than 100 microM. KF-14363 significantly inhibited active oxygen production in peritoneal exudate cells (PEEC) stimulated with arachidonic acid, A23187 and carbon tetrachloride (CCl4) at concentrations over 10 microM, 100 microM and 1 microM, respectively. It tended to inhibit formyl-methionyl-leucyl-phenylalanine-stimulated production of active oxygen in PEEC at concentrations over 10 microM, but there was no significant difference owing to large dispersion. Superoxide dismutase (SOD, 10(4) U/ml) significantly inhibited CCl4-stimulated production of active oxygen in PEEC. KF-14363 inhibited the radical production from CCl4 in the presence of a 9000 x g supernatant fraction of the rat liver which was administered with enzyme induction compounds (S9 mix). SOD (10(4) U/ml) was not effective in this system. In conclusion, KF-14363 inhibited active oxygen production in PEEC induced by various stimulants and also the radical formation from CCl4 in the presence of S9 mix solution.
Yoshitake
I
I
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kubo
K
K
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000378:metabolism; D001552:Benzazepines / Q000627:therapeutic use*; D001685:Biological Factors / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000627:therapeutic use*
D001552:Benzazepines; D001685:Biological Factors; D005609:Free Radicals; D008054:Lipid Peroxides; D013844:Thiazoles; C074412:KF 14363; D002251:Carbon Tetrachloride; D010100:Oxygen