Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure
This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfus...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5281267 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832561408444727296 |
|---|---|
| author | C. Di Filippo B. Ferraro R. Maisto M. C. Trotta N. Di Carluccio S. Sartini C. La Motta F. Ferraraccio F. Rossi M. D’Amico |
| author_facet | C. Di Filippo B. Ferraro R. Maisto M. C. Trotta N. Di Carluccio S. Sartini C. La Motta F. Ferraraccio F. Rossi M. D’Amico |
| author_sort | C. Di Filippo |
| collection | DOAJ |
| description | This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 μM, 0.05 μM, and 0.1 μM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 μM, 0.05 μM, and 0.1 μM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 μM and by 32% for BF-5m 0.1 μM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 μM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP. |
| format | Article |
| id | doaj-art-18c42a21913e40af8844a7b19f9f3fd6 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-18c42a21913e40af8844a7b19f9f3fd62025-02-03T01:25:03ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/52812675281267Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion PressureC. Di Filippo0B. Ferraro1R. Maisto2M. C. Trotta3N. Di Carluccio4S. Sartini5C. La Motta6F. Ferraraccio7F. Rossi8M. D’Amico9Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli”, Second University of Naples, 80138 Naples, ItalyThis study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 μM, 0.05 μM, and 0.1 μM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 μM, 0.05 μM, and 0.1 μM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 μM and by 32% for BF-5m 0.1 μM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 μM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP.http://dx.doi.org/10.1155/2016/5281267 |
| spellingShingle | C. Di Filippo B. Ferraro R. Maisto M. C. Trotta N. Di Carluccio S. Sartini C. La Motta F. Ferraraccio F. Rossi M. D’Amico Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure Journal of Diabetes Research |
| title | Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure |
| title_full | Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure |
| title_fullStr | Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure |
| title_full_unstemmed | Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure |
| title_short | Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure |
| title_sort | effects of the new aldose reductase inhibitor benzofuroxane derivative bf 5m on high glucose induced prolongation of cardiac qt interval and increase of coronary perfusion pressure |
| url | http://dx.doi.org/10.1155/2016/5281267 |
| work_keys_str_mv | AT cdifilippo effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT bferraro effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT rmaisto effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT mctrotta effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT ndicarluccio effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT ssartini effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT clamotta effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT fferraraccio effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT frossi effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure AT mdamico effectsofthenewaldosereductaseinhibitorbenzofuroxanederivativebf5monhighglucoseinducedprolongationofcardiacqtintervalandincreaseofcoronaryperfusionpressure |