- Email: [email protected]
Effect of GCEE or GCEE-loaded microspheres Administration on the Levels of Glutathione and Thiol Redox Molecules in Rat Brain
D. Rossin et al. / Free Radical Biology and Medicine 108 (2017) S18–S107
P-064
Zero-valent Iron Nanoparticles Inhibited Head and Neck Cancer Cells Growth: A Pilot Evaluation and Mechanistic Characterization Kuang-Jing Huang 1, Shang-Rung Wu 1,2, Dar-Bin Shieh 1,2,3 1
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 70101, Taiwan 2 Institute of Oral Medicine, National Cheng Kung University, Tainan, 70101, Taiwan 3 Department of Stomatology, National Cheng Kung University Hospital, 70101, Taiwan Keywords: Zero-valent Iron; ROS stress; lipid peroxidation
Nanomaterials were already identified to exhibit anti-cancer property without carrying drugs. We previously revealed the selective anti-cancer activity of Fe@Au nanoparticles (NP) by impairing mitochondria. The zero-valent iron (ZVI) core contributes the major cytotoxicity. Here, we screen oral cancer cells for resistance profile to ZVI NP and identify OECM1, OC3 and SCC9 to be sensitive, while HSC3, SAS and OC2 tolerate ZVI NP. Resistance clones of OECM1 also can be derived by pulsed NPs treatment. We identify that ZVI NP initiated Fenton reaction and induced free radicals with distinct difference in the mitochondria or cytosol between the refractory and sensitive cancer cells. Lipid peroxidation plays critical roles in the ZVI NP derived ROS induction and subsequent declined mitochondrial respiration. We further discovered the decrease of GPx upon ZVI treatment. GPx inhibitors and glutathione deprivation are able to sensitize ZVI refractory cancer cells accompanied by enhancing mitochondrial depolarization. These results reveal a potential anti-cancer mechanism of ZVI. We also demonstrate how to manipulate the ZVI resistance by combination therapy. This study provides biomarkers that predicts ZVI NP efficacy and new strategies to overcome ZVI resistance through integration of small molecular inhibitors in such new generational anti-cancer nanomedicine.
S39
Keywords: γ-glutamylcysteine ethyl ester; glutathione; thiol redox molecules; drug delivery to brain
It is known that activity of thiol redox molecules such as Trx, TrxR and Ref-1 is regulated by glutathione (GSH). γ-glutamylcysteine ethyl ester (GCEE) is a precursor of GSH biosynthesis and neuroprotective agent. Little is known about boosting or regulating capacity of GCEE or its pharmaceutical preparations for GSH levels or thiol redox molecules in rat brain under normal physiological conditions. Experimentally GCEE (10 mg/kg/daily) was administered to the rats as acute or chronic (five consecutive days). GSH levels determined in brain tissues by DTNB-GSH reductase assay. Trx, TrxR and Ref-1 mRNAs were quantified by qPCR. Lipid/ water/lipid technique was used for the preparation of GCEE- loaded microspheres and administered to the rats with the dose of 2 mg/ml. Following the administration of GCEE- loaded microspheres, the levels of GSH in hippocampus and cortex regions were determined at 12 different time periods ranging 0–96 h by HPLC pharmacokinetically. Acute or chronic treatments with GCEE significantly increased GSH levels, and Trx mRNA expression was the most regulated parameter. Pharmacokinetically the most remarkable change in GSH levels in brain tissues was observed at 4– 6 h. As a conclusion, GCEE is able to regulate the levels of GSH and thiol redox parameters, and GCEE-loaded microspheres can be used to deliver this agent to the brain successfully. E-mail address: [email protected] (A. Yalcin) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.150
P-066
Validation study of a food frequency questionnaire for the measurement of food consumption in polyphenols: use of a urinary bioamarker. Preliminary results
E-mail address: [email protected] (K.-J. Huang)
Axelle Hoge 1, Michele Guillaume 1, Anne -Françoise Donneau 1, Adelin Albert 1, Jean - Paul Cheramy-bien 2, Jessica Tabart 3, Claire Kevers 3, Jacques Dommes 3, Jean - Olivier Defraigne 2, Joel Pincemail 2
Acknowledgements
1
This work was supported by the grant MOST104-2627-M006 and MOST 105–2627-M006 from the Ministry of Science and Technology of Taiwan.
2
http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.149
Department of Public Health Sciences, University of Liège, Belgium Departement of Cardiovascular Surgery, Credec, Plateforme Nutrition Antioxydante et Santé, CHU of Liège, Belgium 3 Plant Molecular Biology and Biotechnology Unit and CEDEVIT, University of Liège, Belgium Keywords: Polyphenol; FFQ; urinary biomarker
P-065
Effect of GCEE or GCEE-loaded microspheres Administration on the Levels of Glutathione and Thiol Redox Molecules in Rat Brain Ayfer Yalcin 1, Sinem Ezgi Turunc 1, Gulbeyaz Yildiz Turkyilmaz 2, Lutfiye Kanit 3, Ercument Karasulu 2 1
Ege University, Faculty of Pharmacy, Dept.of Biochemistry, Izmir, Turkey 2 Ege University, Faculty of Pharmacy, Dept.of Pharmaceutical Technology, Izmir, Turkey 3 Ege University, Faculty of Medicine, Dept.of Physiology, Izmir, Turkey
The purpose of our study was to assess the validity of the food frequency questionnaire (FFQ) used in the NESCaV study (Nutrition, Environment and Cardiovascular Health) for the measurement of food polyphenols intake. 53 volunteer adults, aged between 20 and 60, were included in the Stroxybio study*. The nutritional intake of total polyphenols estimated from the FFQ was compared with the results obtained from a 3-day dietary recording (EA) as well as the total polyphenol urine concentrations determined by the Folin-Ciocalteu method. The polyphenol feed composition was estimated using the Phenol-Explorer database. The median intakes of polyphenols estimated from FFQ and EA were 2270.92 mg per day and 1203.63 mg per day, respectively. The median urinary concentrations of polyphenols are 10678.57 μg of gallic acid equivalent per gram of creatinine. The results show that there was a strong association between the results of the two dietary questionnaires, FFQ and EA (r¼0.633,
P-064
Zero-valent Iron Nanoparticles Inhibited Head and Neck Cancer Cells Growth: A Pilot Evaluation and Mechanistic Characterization Kuang-Jing Huang 1, Shang-Rung Wu 1,2, Dar-Bin Shieh 1,2,3 1
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, 70101, Taiwan 2 Institute of Oral Medicine, National Cheng Kung University, Tainan, 70101, Taiwan 3 Department of Stomatology, National Cheng Kung University Hospital, 70101, Taiwan Keywords: Zero-valent Iron; ROS stress; lipid peroxidation
Nanomaterials were already identified to exhibit anti-cancer property without carrying drugs. We previously revealed the selective anti-cancer activity of Fe@Au nanoparticles (NP) by impairing mitochondria. The zero-valent iron (ZVI) core contributes the major cytotoxicity. Here, we screen oral cancer cells for resistance profile to ZVI NP and identify OECM1, OC3 and SCC9 to be sensitive, while HSC3, SAS and OC2 tolerate ZVI NP. Resistance clones of OECM1 also can be derived by pulsed NPs treatment. We identify that ZVI NP initiated Fenton reaction and induced free radicals with distinct difference in the mitochondria or cytosol between the refractory and sensitive cancer cells. Lipid peroxidation plays critical roles in the ZVI NP derived ROS induction and subsequent declined mitochondrial respiration. We further discovered the decrease of GPx upon ZVI treatment. GPx inhibitors and glutathione deprivation are able to sensitize ZVI refractory cancer cells accompanied by enhancing mitochondrial depolarization. These results reveal a potential anti-cancer mechanism of ZVI. We also demonstrate how to manipulate the ZVI resistance by combination therapy. This study provides biomarkers that predicts ZVI NP efficacy and new strategies to overcome ZVI resistance through integration of small molecular inhibitors in such new generational anti-cancer nanomedicine.
S39
Keywords: γ-glutamylcysteine ethyl ester; glutathione; thiol redox molecules; drug delivery to brain
It is known that activity of thiol redox molecules such as Trx, TrxR and Ref-1 is regulated by glutathione (GSH). γ-glutamylcysteine ethyl ester (GCEE) is a precursor of GSH biosynthesis and neuroprotective agent. Little is known about boosting or regulating capacity of GCEE or its pharmaceutical preparations for GSH levels or thiol redox molecules in rat brain under normal physiological conditions. Experimentally GCEE (10 mg/kg/daily) was administered to the rats as acute or chronic (five consecutive days). GSH levels determined in brain tissues by DTNB-GSH reductase assay. Trx, TrxR and Ref-1 mRNAs were quantified by qPCR. Lipid/ water/lipid technique was used for the preparation of GCEE- loaded microspheres and administered to the rats with the dose of 2 mg/ml. Following the administration of GCEE- loaded microspheres, the levels of GSH in hippocampus and cortex regions were determined at 12 different time periods ranging 0–96 h by HPLC pharmacokinetically. Acute or chronic treatments with GCEE significantly increased GSH levels, and Trx mRNA expression was the most regulated parameter. Pharmacokinetically the most remarkable change in GSH levels in brain tissues was observed at 4– 6 h. As a conclusion, GCEE is able to regulate the levels of GSH and thiol redox parameters, and GCEE-loaded microspheres can be used to deliver this agent to the brain successfully. E-mail address: [email protected] (A. Yalcin) http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.150
P-066
Validation study of a food frequency questionnaire for the measurement of food consumption in polyphenols: use of a urinary bioamarker. Preliminary results
E-mail address: [email protected] (K.-J. Huang)
Axelle Hoge 1, Michele Guillaume 1, Anne -Françoise Donneau 1, Adelin Albert 1, Jean - Paul Cheramy-bien 2, Jessica Tabart 3, Claire Kevers 3, Jacques Dommes 3, Jean - Olivier Defraigne 2, Joel Pincemail 2
Acknowledgements
1
This work was supported by the grant MOST104-2627-M006 and MOST 105–2627-M006 from the Ministry of Science and Technology of Taiwan.
2
http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.149
Department of Public Health Sciences, University of Liège, Belgium Departement of Cardiovascular Surgery, Credec, Plateforme Nutrition Antioxydante et Santé, CHU of Liège, Belgium 3 Plant Molecular Biology and Biotechnology Unit and CEDEVIT, University of Liège, Belgium Keywords: Polyphenol; FFQ; urinary biomarker
P-065
Effect of GCEE or GCEE-loaded microspheres Administration on the Levels of Glutathione and Thiol Redox Molecules in Rat Brain Ayfer Yalcin 1, Sinem Ezgi Turunc 1, Gulbeyaz Yildiz Turkyilmaz 2, Lutfiye Kanit 3, Ercument Karasulu 2 1
Ege University, Faculty of Pharmacy, Dept.of Biochemistry, Izmir, Turkey 2 Ege University, Faculty of Pharmacy, Dept.of Pharmaceutical Technology, Izmir, Turkey 3 Ege University, Faculty of Medicine, Dept.of Physiology, Izmir, Turkey
The purpose of our study was to assess the validity of the food frequency questionnaire (FFQ) used in the NESCaV study (Nutrition, Environment and Cardiovascular Health) for the measurement of food polyphenols intake. 53 volunteer adults, aged between 20 and 60, were included in the Stroxybio study*. The nutritional intake of total polyphenols estimated from the FFQ was compared with the results obtained from a 3-day dietary recording (EA) as well as the total polyphenol urine concentrations determined by the Folin-Ciocalteu method. The polyphenol feed composition was estimated using the Phenol-Explorer database. The median intakes of polyphenols estimated from FFQ and EA were 2270.92 mg per day and 1203.63 mg per day, respectively. The median urinary concentrations of polyphenols are 10678.57 μg of gallic acid equivalent per gram of creatinine. The results show that there was a strong association between the results of the two dietary questionnaires, FFQ and EA (r¼0.633,