Biofactors - Volume 16, issue 3-4

Authors: Tsuchiya, Hironori | Nagayama, Motohiko | Tanaka, Toshiyuki | Furusawa, Miyuki | Kashimata, Masanori | Takeuchi, Hiroshi

Article Type: Research Article

Abstract: Since several anti-cancer drugs interact with cell membrane lipids, the effects of anti-cancer dietary factors on liposomal membranes with different lipid composition were comparatively studied by measuring fluorescence polarization. Fluidity was imparted on both hydrophobic and hydrophilic regions of lipid bilayers by decreasing cholesterol and increasing unsaturated phosphatidylcholine in membranes. At 0.625–10 μM, (–)-epigallocatechin gallate, genistein, apigenin, resveratrol and a reference anti-cancer drug, doxorubicin, rigidified the tumor cell …model membranes consisting of 20 mol% cholesterol and 80 mol% phosphatidylcholine with the acyl chain 18:1/16:0 ratio of 1.0, but not daidzein. They were more effective on the membrane core than the membrane surface. Quercetin showed a biphasic effect on the hydrophobic regions of membrane lipid bilayers to rigidify above 5 μM and fluidize below 2.5 μM. In contrast, anti-cancer dietary factors and doxorubicin were not or much less effective in rigidifying the normal cell model membranes consisting of 40 mol% cholesterol and 60 mol% phosphatidylcholine with the acyl chain 18:1/16:0 ratio of 0.5. The membrane-rigidifying effects were greater depending on a decrease of the cholesterol/phosphatidylcholine ratio and an increase of the phosphatidylcholine unsaturation degree. Membrane-active dietary factors and doxorubicin inhibited the growth of mouse myeloma cells at 10–100 μM, while the growth inhibition by membrane-inactive daidzein was relatively weak. Anti-cancer dietary factors appear to act on more fluid membranes like tumor cells as well as doxorubicin to induce rigidification, especially in the hydrocarbon core of membrane lipids, which is determined by the composition of cholesterol and unsaturated phospholipids. Show more

Keywords: anti-cancer dietary factor, liposomal membrane, fluidity, membrane-rigidifying effect, lipid composition

Citation: BioFactors, vol. 16, no. 3-4, pp. 45-56, 2002

Authors: Ichikawa, Makoto | Ryu, Kenjiro | Yoshida, Jiro | Ide, Nagatoshi | Yoshida, Susumu | Sasaoka, Takashi | Sumi, Shin-Ichiro

Article Type: Research Article

Abstract: 1,2,3,4-Tetrahydro-β-carboline derivatives (THβCs) are formed through Pictet-Spengler chemical condensation between tryptophan and aldehydes during food production, storage and processing. In the present study, in order to identify the antioxidants in aged garlic extract (AGE), we fractionated it and identified four THβCs; 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids (MTCC) and 1-methyl-1,2,3,4-tetrahydro-β-carboline-1,3-dicarboxylic acid (MTCdiC) in both diastereoisomers using liquid chromatography mass spectrometry (LC-MS). Interestingly, these compounds …were not detected in raw garlic, but the contents increased during the natural aging process of garlic. In in vitro assay systems, all of these compounds have shown strong hydrogen peroxide scavenging activities. (1S, 3S)-MTCdiC was found to be stronger than the common antioxidant, ascorbic acid. MTCC and MTCdiC inhibited AAPH-induced lipid peroxidation. Both MTCdiCs also inhibited LPS-induced nitrite production from murine macrophages at 10–100 μM. Our data suggest that these compounds are potent antioxidants in AGE, and thus may be useful for prevention of disorders associated with oxidative stress. Show more

Keywords: aged garlic extract, tetrahydro-β-carboline derivatives, Maillard reaction products, antioxidant, LC-MS

Citation: BioFactors, vol. 16, no. 3-4, pp. 57-72, 2002

Authors: Murakami, Akira | Koshimizu, Koichi | Ohigashi, Hajime | Kuwahara, Shigeru | Kuki, Wataru | Takahashi, Yasuo | Hosotani, Keisuke | Kawahara, Satsuki | Matsuoka, Yumi

Article Type: Research Article

Abstract: Nobiletin (NOB), a polymethoxyflavonoid, is an effective anti-inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of NOB with those of luteolin (LT) in male SD rats. Each flavonoid (67.1 μmol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, NOB showed a notable tendency for localizing into the …mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both NOB and LT were completely excreted within 24 hours. Further, significant amounts of NOB were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of NOB from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono-demethylated NOB, including 3'-demethyl-NOB, and two di-demethylated types, as well as 3'-demethyl-NOB alone in serum samples using liquid chromatography-mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue. Show more

Keywords: nobiletin, luteolin, flavonoid, metabolism, conjugation

Citation: BioFactors, vol. 16, no. 3-4, pp. 73-82, 2002

Authors: Shahrzad, Siranoush | Cadenas, Enrique | Sevanian, Alex | Packer, Lester

Article Type: Research Article

Abstract: Water-dispersible beadlets of carotenoids were used as supplements for human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs) and human monocytes. Stability, cellular association and cytotoxicity of the carotenoid beadlets were compared with carotenoids delivered with tetrahydrofuran (THF). Incubations with lycopene, β-carotene, lutein and astaxanthin dissolved in THF resulted in a lower stability in the medium, lower cellular association, and a higher standard deviation. Beadlets provided 60, 4, 6, …and 2 times greater accumulation of lycopene, β-carotene, lutein and astaxanthin, respectively, by PBMCs than THF. The cellular association of carotenoids delivered by THF seems to be more carotenoid-specific than when carotenoids are delivered by beadlets. After 48~h of incubation under cell culture conditions all of the four carotenoids (1 μM) delivered by beadlets to the medium showed a reduction less than 30%. In addition, no cytotoxic effect of the carotenoid beadlets or the vehicle alone was detected in a concentration range of 0.5–5 μM. The results show that beadlets are a non-toxic vehicle for supplementing and stabilizing carotenoids in culture media offering a reasonable compromise in term of cell accumulation efficiency. Show more

Keywords: carotenoids, water-dispersible beadlets, β-carotene, lycopene, lutein, astaxanthin

Citation: BioFactors, vol. 16, no. 3-4, pp. 83-91, 2002

Authors: Yoshida, Yasukazu | Niki, Etsuo

Article Type: Research Article

Abstract: Carboxyethyl-6-hydroxychromans (CEHC), the major metabolites of both tocopherols (Toc) and tocotrienols (Toc-3), have been found in human plasma. In the present study, the antioxidant properties of α- and γ-CEHC were measured and compared with α- and γ- tocopherols. Following results were obtained: (1)α- and γ-CEHC have the same reactivities toward radicals and exert the same antioxidant activities against lipid peroxidation in organic solution as the corresponding parent tocopherols …respectively; (2) the partition coefficient decreased in the order α-Toc (3.36) > γ-Toc (3.14) > α-CEHC (2.26) > pentamethyl-6-chromanol (1.92) > γ-CEHC (1.83) > 0 > Trolox (-0.97); (3) α- and γ-CEHC scavenge aqueous radicals more efficiently but they inhibit the lipid peroxidation within the membranes less efficiently than the corresponding α- and γ-Toc, respectively; (4) α-CEHC inhibits the oxidation synergistically with ascorbate; and (5) α- andγ-CEHC reduce Cu(II) to give Cu(I) and corresponding quinones as major product, but the prooxidant effect of CEHC in the presence of cupric ion was small. These results imply that CEHC may act as an antioxidant in vivo especially for those who take tocopherol supplement. Show more

Keywords: antioxidant, lipid peroxidation, tocopherol, carboxyethyl-6-hydroxychroman, copper, synergistic antioxidant effect

Citation: BioFactors, vol. 16, no. 3-4, pp. 93-103, 2002

Authors: Minamiyama, Yukiko | Takemura, Shigekazu | Toyokuni, Shinya | Nishino, Yoshihiro | Yamasaki, Keiichi | Hai, Seikan | Yamamoto, Satoshi | Okada, Shigeru

Article Type: Research Article

Abstract: The most noticeable hypothesis regarding the pathogenesis of cisplatin toxicity, seen mainly in kidney and intestine, is oxidative stress, an imbalance between free-radical generating cisplatin and radical scavenging systems. This paper describes the role of the antioxidant system in cisplatin-induced toxicity and the protective effect by a processed grain food (Antioxidant Biofactor: AOB®), which has been shown to exhibit strong antioxidant activity. Male Fischer 344 rats were used. They were pre-fed either a basal …diet (control, 15 g/day) or the diet supplemented with AOB® to provide 6.5% or 20% of total diet throughout the experiment. Cisplatin (5~mg/kg, i.v.) was administered at the start of the experiment, and the animals were sacrificed 5 days later. Blood urea nitrogen (BUN) and plasma creatinine, NO_2^{-} and NO_3^{-} (NOx) were determined from the plasma. The levels of 4-hydroxy-2-nonenal (a lipid peroxidation product), 8-hydroxy-deoxyguanosine (8-OHdG, an oxidatively modified DNA adduct) and nitrotyrosine were histologically analyzed. The cisplatin administration resulted in a loss of body weight and elevations of BUN, serum creatinine and NOx levels, whereas AOB supplement reversed these effects. The severe morphological damages induced in the kidney and intestine by the cisplatin administration were markedly improved in the AOB group. The levels of lipid peroxidation, 8-OHdG, and nitrotyrosine all paralleled the morphological damage. The AOB effect was dose dependent. In conclusion, the present study suggests that certain food additives like AOB may be of benefit against the side effects of cisplatin. Show more

Keywords: antioxidant, cisplatin damage, oxidative stress, rats

Citation: BioFactors, vol. 16, no. 3-4, pp. 105-115, 2002