論文

The effects of hexasulfobutylated C60 (FC4S) and monomalonic acid C60 (MMA C60), the fullerene C60 derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C60 (10 μmol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C60 (10 μmol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC4S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC4S (10 μmol/l). In the denuded aortic rings, FC4S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC4S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 μmol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC4S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium. Copyright © 2002 S. Karger AG, Basel.

Fullerene derivatives which have carboxylic acid moiety effectively inhibited glutathione reductase activity. Preincubation of the reductase and fullerene derivative at 37°C enhanced the inhibition activity.

Inhibitory effects of newly synthesized fullerene C60 derivatives 1 (C60-bis(N,N-dimethylpyrrolidinium iodide)), 2 (C60-proline-N-acetic acid) and 3 (C60-ethylenediamine-N, N′-diacetic acid) on acetylcholine-induced relaxation in endothelium-intact rabbit thoracic aorta precontracted by phenylephrine (10-6 M) were studied. Fullerene C60 derivative 1 (3 × 10-6 M), 2 (10-5 M) and 3 (10-5 M) reduced the maximum amplitude of the acetylcholine-induced relaxation without significantly changing the pD2 values obtained from the concentration - response curves. In the presence of fullerene C60 derivative 1 (10-5 M) the acetylcholine-induced relaxation was eliminated and an acetylcholine-induced contraction was observed. These results suggest that fullerene C60 derivative 1 strongly inhibits endothelium (nitric oxide)-dependent acetylcholine-induced relaxation in thoracic aorta of rabbit.

Focusing on α-pyridoin (1, 1,2-di(2-pyridyl)-1,2-ethenediol) as the lead compound of the novel antioxidative enediol, we synthesized 5,5′- or 6,6′-bis-substituted derivatives of 1 from disubstituted pyridines. The antioxidant activity of 1 and its synthetic derivatives 2-7 was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) scavenging assay and inhibition of lipid peroxidation. In the DPPH assay, 1 exhibited an activity stronger than that of ascorbic acid, and 5,5′-dimethyl-(5) or 5,5′-dimethoxy- substituted derivatives (6) exhibited more potent activity than 1. The DPPH scavenging activities of α-pyridoins were correlated with their oxidation potential and thus the electron density of enediol. 5 and 6 effectively inhibited lipid peroxidation in the rat liver microsome/tert-butyl hydroperoxide system. Therefore, 5 and 6 serve as good candidates for a pharmacologically useful enediol antioxidant. © 2005 Elsevier Ltd. All rights reserved.

The aim of this study was to evaluate the potential role of polyglycolic acid (PGA), poly(glycolic acid-ε-caprolactone) (PGCL), poly(l-lactic acid-glycolic acid) (PLGA), poly(l-lactic acid-ε-caprolactone, 75:25 (w/w)) [P(LA-CL)25], poly-ε-caprolactone (tetrabutoxy titanium) [PCL(Ti)], and fullerene C-60 dimalonic acid (DMA) in cartilage transplants. After 4 weeks of culture of human articular cartilage, the levels of cell proliferation and differentiation and the expression of cartilage-specific matrix genes were estimated. The relationship between cell differentiation and gap junction protein connexin 43 (Cx43) was also evaluated. All materials except PCL(Ti) retained cell proliferation activities similar to the controls. Cell differentiation levels from the highest to the lowest were in the following order: PGA >> PLGA > PGCL > Control = DMSO > P(LA-CL)25 = PCL(Ti) >> fullerene C-60 DMA. Expression of the collagen type II gene was selectively upregulated for PGA, PGCL, and PLGA and slightly increased for P(LA-CL)25 polymers but was downregulated for fullerene C-60 DMA. Aggrecan gene expression was strongest with PGA and was consistently expressed with other matrices, especially with PGCL and PLGA. However, the expression patterns of the connexin 43 gene were different from the former two genes. Multiple regression analysis revealed a high correlation between cartilage proteoglycans production and expression levels of these three genes. © The Japanese Society for Artificial Organs 2005.

Fine whiskers of a C60 derivative, i.e., C60 monosubstituted by ethyl ester of malonic acid, C60[C(COOC 2H5)2], were fabricated for the first time using a system of toluene with concentrated C60[C(COOC 2H5)2] and isopropyl alcohol. The center-to-center distance of C60[C(COOC2H 5)2] molecules along the close-packed direction of the C60[C(COOC2H5)2] whiskers was in the same range as that of the C60 nanowhiskers prepared by the same method. The C60[C(COOC2H5)2] whiskers were assumed to take body-centered tetragonal or hexagonal close-packed crystal structures. The C60[C(COOC2H 5)2] whiskers showed a high density of stacking faults. The C60[C(COOC2H5)2] whiskers with the growth direction different from the C60 whiskers were observed.