The effect of a synthetic cyclic disulfide compound, SA3443, on neovascularization was investigated. In vitro, enzyme-linked immunosorbent assay and RT-PCR demonstrated that SA3443 suppressed the expression of the hypoxia-induced vascular endothelial growth factor (VEGF) at both protein and mRNA levels in ARPE-19 cells. In vivo, the administration of SA3443 to mice with laser-induced choroidal neovascularization (CNV) suppressed the leakage from the lesions and reduced their size. Furthermore, the expression level of VEGF protein was significantly reduced by the administration of SA3443. Taken together, our results demonstrate that SA3443 suppresses VEGF production and reduces vascular leakage and the growth of mouse experimental CNV.
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Suppression of laser-induced choroidal neovascularization by oral administration of SA3443 in mice.
FEBS Lett
November 2005
Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
The effect of a synthetic cyclic disulfide compound, SA3443, on neovascularization was investigated. In vitro, enzyme-linked immunosorbent assay and RT-PCR demonstrated that SA3443 suppressed the expression of the hypoxia-induced vascular endothelial growth factor (VEGF) at both protein and mRNA levels in ARPE-19 cells. In vivo, the administration of SA3443 to mice with laser-induced choroidal neovascularization (CNV) suppressed the leakage from the lesions and reduced their size.
View Article and Find Full Text PDFDifferent pharmacokinetics of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-(3-14C)dithiazocine-4-carboxyli c acid between the fasting and non-fasting rat: role of intestinal microorganisms.
Xenobiotica
January 1998
Discovery Research Division, Santen Pharmaceutical Co., Ltd, Osaka, Japan.
1. We report differences in the pharmacokinetics of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-(3-14C)dithiazocine-4-carb oxylic acid (14C-SA3443) between the normal fasting and non-fasting rat, especially in the blood concentration-time curves and respiratory excretion. Exhalation of 14CO2 was an important route of elimination and accounted for 21.
View Article and Find Full Text PDFPreventive effect of SA3443, a novel cyclic disulfide, on glucocorticoid-induced cataract formation of developing chick embryo.
Exp Eye Res
June 1994
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
The preventive effect of SA3443 [(4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid] against glucocorticoid-induced cataract of developing chick embryos was studied. When hydrocortisone succinate sodium (HC: 0.25 mumol per egg) was administered to 15-day-old embryos, almost all lenses became opaque (stage I:O%, II: 2.
View Article and Find Full Text PDFThe inhibitory effect of SA3443, a novel cyclic disulfide compound, on alpha-naphthyl isothiocyanate-induced intrahepatic cholestasis in rats.
Clin Exp Pharmacol Physiol
September 1993
Central Research Laboratories, Santen Pharmaceutical Co. Ltd, Osaka, Japan.
1. We investigated the effect of SA3443, a novel cyclic disulfide compound, on alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in rats. 2.
View Article and Find Full Text PDFSA3443, a novel cyclic disulfide compound, depresses anti-SRBC antibody-forming cell responses in the mouse through inhibition of antigen-presenting cell activities.
Drugs Exp Clin Res
April 1992
Central Research Laboratories, Santen Pharmaceutical Co., Osaka, Japan.
(4R)-Hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which has potential hepatoprotective properties. The effect of SA3443 on the induction of anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFC) responses was investigated in vivo and in vitro. SA3443 (approximately 3 mg/kg/day) remarkably decreased the number of anti-SRBC PFC in the spleens of mice immunized with a high dose of SRBC in vivo.
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