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Papi A Orlandi M Bartolini G Barillari J Iori R Paolini M Ferroni F Grazia Fumo M Pedulli GF Valgimigli L 《Journal of agricultural and food chemistry》2008,56(3):875-883
There is high current interest in the chemopreventive potential of Brassica vegetables (cruciferae), particularly due to their content in glucosinolates (GL), which upon myrosinase hydrolysis release the corresponding isythiocyanates (ITC). Some ITCs, such as sulforaphane (SFN) from broccoli ( Brassica oleacea italica), have been found to possess anticancer activity through induction of apoptosis in selected cell lines, as well as indirect antioxidant activity through induction of phase II detoxifying enzymes. Japanese daikon ( Raphanus sativus L.) is possibly the vegetable with the highest per capita consumption within the Brassicaceae family. Thanks to a recently improved gram scale production process, it was possible to prepare sufficient amounts of the GL glucoraphasatin (GRH) as well as the corresponding ITC 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) from its sprouts. This paper reports a study on the cytotoxic and apoptotic activities of GRH-ITC compared with the oxidized counterpart 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC) on three human colon carcinoma cell lines (LoVo, HCT-116, and HT-29) together with a detailed kinetic investigation of the direct antioxidant/radical scavenging ability of GRH and GRH-ITC. Both GRH-ITC and GRE-ITC reduced cell proliferation in a dose-dependent manner and induced apoptosis in the three cancer cell lines. The compounds significantly ( p < 0.05) increased Bax and decreased Bcl2 protein expression, as well as producing caspase-9 and PARP-1 cleavage after 3 days of exposure in the three cancer cell lines. GRH-ITC treatment was shown to have no toxicity with regard to normal human lymphocytes (-15 +/- 5%) in comparison with SFN (complete growth inhibition). GRH and GRH-ITC were able to quench the 2,2-diphenyl-1-picrylhydrazyl radical, with second-order rate constants of 14.0 +/- 2.8 and 43.1 +/- 9.5 M(-1) s(-1), respectively (at 298 K in methanol), whereas the corresponding value measured here for the reference antioxidant alpha-tocopherol was 425 +/- 40 M (-1) s (-1). GRH reacted with H2O2 and tert-butyl hydroperoxide in water (pH 7.4) at 37 degrees C, with rate constants of 1.9 +/- 0.3 x 10(-2) and 9.5 +/- 0.3 x 10(-4) M(-1) s (-1) (paralleling recently developed synthetic antioxidants) being quantitatively (>97%) converted to GRE. It is demonstrated that GRH-ITC has interesting antioxidant/radical scavenging properties, associated with a selective cytotoxic/apoptotic activity toward three human colon carcinoma cell lines, and very limited toxicity on normal human T-lymphocytes. 相似文献
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Monari M. Foschi J. Bichi Ruspoli Forteguerri E. Valgimigli S. Zanatta M. Capitani O. Serrazanetti G. P. 《Veterinary research communications》2009,33(8):1045-1045
Veterinary Research Communications - 相似文献
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Barillari J Canistro D Paolini M Ferroni F Pedulli GF Iori R Valgimigli L 《Journal of agricultural and food chemistry》2005,53(7):2475-2482
Rocket (Eruca sativa Mill. or Eruca vesicaria L.) is widely distributed all over the world and is usually consumed fresh (leafs or sprouts) for its typical spicy taste. Nevertheless, it is mentioned in traditional pharmacopoeia and ancient literature for several therapeutic properties, and it does contain a number of health promoting agents including carotenoids, vitamin C, fibers, flavonoids, and glucosinolates (GLs). The latter phytochemicals have recently gained attention as being the precursors of isothiocyanates (ITCs), which are released by myrosinase hydrolysis during cutting, chewing, or processing of the vegetable. ITCs are recognized as potent inducers of phase II enzymes (e.g., glutathione transferases, NAD(P)H:quinone reductase, epoxide hydrolase, etc.), which are important in the detoxification of electrophiles and protection against oxidative stress. The major GL found in rocket seeds is glucoerucin, GER (108 +/- 5 micromol g(-)(1) d.w.) that represents 95% of total GLs. The content is largely conserved in sprouts (79% of total GLs), and GER is still present to some extent in adult leaves. Unlike other GLs (e.g., glucoraphanin, the bio-precursor of sulforaphane), GER possesses good direct as well as indirect antioxidant activity. GER (and its metabolite erucin, ERN) effectively decomposes hydrogen peroxide and alkyl hydroperoxides with second-order rate constants of k(2) = 6.9 +/- 0.1 x 10(-)(2) M(-)(1) s(-)(1) and 4.5 +/- 0.2 x 10(-)(3) M(-)(1) s(-) , respectively, in water at 37 degrees C, thereby acting as a peroxide-scavenging preventive antioxidant. Interestingly, upon removal of H(2)O(2) or hydroperoxides, ERN is converted into sulforaphane, the most effective inducer of phase II enzymes among ITCs. On the other hand, ERN (and conceivably GER), like other ITCs, does not possess any chain-breaking antioxidant activity, being unable to protect styrene from its thermally (37 degrees C) initiated autoxidation in the presence of AMVN. The mechanism and relevance of the antioxidant activity of GER and ERN are discussed. 相似文献
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Solvent extracts from the aerial and root parts and seed oil from E. sativa (rocket salad) were assayed for anticancer activity against melanoma cells. The seed oil (isothiocyanates rich) significantly (p < 0.01) reduced the tumor growth comparable to the control. Remarkably, the seed oil inhibited melanoma growth and angiogenesis in mice without any major toxicity. The findings qualify seed oil for further investigations in the real of cancer prevention and treatment. 相似文献
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Andrea Barbarossa Julie Rambaldi Massimo Giunti Anna Zaghini Marco Cunto Daniele Zambelli Simond Valgimigli Francesco Santoro Noemi Romagnoli 《Veterinary anaesthesia and analgesia》2017,44(3):435-443
Objective
To investigate the pharmacokinetics of buprenorphine and its main active metabolite, norbuprenorphine, after administration of an intravenous loading dose followed by constant rate infusion (CRI) in dogs.Study design
Prospective, clinical study.Animals
A total of seven healthy dogs undergoing elective ovariectomy.Methods
Buprenorphine was administered as a loading dose (intravenous bolus of 15 μg kg?1) followed by CRI (2.5 μg kg?1 hour?1 for 6 hours). Moreover, intraoperative analgesia was supplemented by an intramuscular carprofen (4 mg kg?1) injection, administered prior to surgery, and by lidocaine, administrated through subcutaneous infiltration and through a splash on the ovarian vascular pedicle during surgery. Pain and sedation were scored for all animals throughout the 24-hour study period and rescue analgesia was administered when a visual analogue scale score was > 40 mm. Blood samples were collected from a jugular catheter at regular intervals, and plasma concentrations of buprenorphine and norbuprenorphine were determined by a validated liquid chromatography–tandem mass spectrometry method.Results
Buprenorphine showed a two-compartment kinetic profile. Maximum concentration was 23.92 ± 8.64 ng mL?1 at 1 minute (maximum time); elimination half-life was 41.87 ± 17.35 minutes; area under the curve was 486.68 ± 125.66 minutes ng?1 mL?1; clearance was 33.61 ± 13.01 mL minute?1 kg?1, and volume of distribution at steady state was 1.77 ± 0.50 L kg?1. In no case was rescue analgesia required. Norbuprenorphine resulted below the lower limit of quantification in almost all samples.Conclusions and clinical relevance
The results suggest that a buprenorphine CRI can be a useful tool for providing analgesia in postoperative patients, considering its minor side effects and the advantages of a CRI compared to frequent boluses. The negligible contribution of norbuprenorphine to the therapeutic effect was confirmed. 相似文献8.
Monari M. Foschi J. Bichi Ruspoli Forteguerri E. Valgimigli S. Zanatta M. Capitani O. Serrazanetti G. P. 《Veterinary research communications》2009,33(1):109-111
Veterinary Research Communications - 相似文献
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Barillari J Iori R Papi A Orlandi M Bartolini G Gabbanini S Pedulli GF Valgimigli L 《Journal of agricultural and food chemistry》2008,56(17):7823-7830
Brassica vegetables are attracting major attention as healthy foods because of their content of glucosinolates (GLs) that release the corresponding isothiocyanates (ITCs) upon myrosinase hydrolysis. A number of studies have so far documented the chemopreventive properties of some ITCs. On the other hand, single nutrients detached from the food itself risk being somewhat "reductive", since plants contain several classes of compounds endowed with a polyhedral mechanism of action. Our recent finding that 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) and 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC), released by the GLs purified from Japanese (Kaiware) Daikon (Raphanus sativus L.) seeds and sprouts, had selective cytotoxic/apoptotic activity on three human colon carcinoma cell lines prompted further research on the potential chemopreventive role of a standardized Kaiware Daikon extract (KDE), containing 10.5% w/w GRH and 3.8% w/w GRE, compared to its isolated components. KDE administered in combination with myrosinase at doses corresponding to 50 microM GRH-ITC plus 15 microM GRE-ITC (50 microM KDE-ITC) to three human cancer cell lines (LoVo, HCT-116 and HT-29) significantly reduced cell growth by 94-96% of control in six days (p < 0.05), outperforming pure GRH-ITC or GRE-ITC at the same dose. On the other hand, the same treatment had no significant toxicity on normal human T-lymphocytes. A 50 microM concentration of KDE-ITC had relevant apoptosis induction in all tested cancer cell lines, as confirmed by annexin V assay (e.g., 33% induction in LoVo compared to control, p < 0.05), Bax protein induction (e.g., +20% in HT-29, p < 0.05), and Bcl2 downregulation (e.g.-20% in HT-29, p < 0.05), and induced caspase-1 and PARP-1 activation in all cancer cells as shown by Western blot analysis. Unlike pure GRH or GRH-ITC, KDE also had significant chain-breaking antioxidant activity, retarding the AAPH-initiated autoxidation of methyl linoleate in SDS micelles at concentrations as low as 4.4 ppm (-50% in oxygen consumption rate), as monitored by Clark-type microelectrode oxygen-uptake kinetics, and induced very fast quenching of DPPH. radical in methanol with t(1/2) (s) = (1.47 +/- 0.25) x 10(-2)/[KDE; (g/L)], measured by stopped-flow UV-vis kinetics at 298 K. The potential chemopreventive role of KDE is discussed. 相似文献
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