Cargando…
Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo
The methylated analogue of the polyphenol resveratrol (RV), 2,3′,4,5′-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promis...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930636/ https://www.ncbi.nlm.nih.gov/pubmed/31795324 http://dx.doi.org/10.3390/molecules24234360 |
_version_ | 1783482938774519808 |
---|---|
author | Zaabalawi, Azziza Astley, Cai Renshall, Lewis Beards, Frances Lightfoot, Adam P. Degens, Hans Whitehead, Debra Alexander, Yvonne Harris, Lynda K Azzawi, May |
author_facet | Zaabalawi, Azziza Astley, Cai Renshall, Lewis Beards, Frances Lightfoot, Adam P. Degens, Hans Whitehead, Debra Alexander, Yvonne Harris, Lynda K Azzawi, May |
author_sort | Zaabalawi, Azziza |
collection | PubMed |
description | The methylated analogue of the polyphenol resveratrol (RV), 2,3′,4,5′-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promising delivery modality for enhanced uptake into tissues. We examined the effect of delivery of TMS in liposomes on the restoration of vasodilator responses of isolated aortic vessels after acute tension elevation ex vivo. Aortic vessels from young male Wistar rats were isolated, and endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) responses assessed. Acute tension elevation (1 h) significantly reduced ACh dilator responses, which were restored following incubation with superoxide dismutase or apocynin (an NADPH oxidase inhibitor). Incubation with TMS-loaded liposomes (mean diameter 157 ± 6 nm; PDI 0.097) significantly improved the attenuated dilator responses following tension elevation, which was sustained over a longer period (4 h) when compared to TMS solution. Endothelial denudation or co-incubation with L-NNA (Nω-nitro-l-arginine; nitric oxide synthase inhibitor) resulted in loss of dilator function. Our findings suggest that TMS-loaded liposomes can restore attenuated endothelial-dependent dilator responses induced by an oxidative environment by reducing NADPH-oxidase-derived ROS and potentiating the release of the vasodilator nitric oxide. TMS-loaded liposomes may be a promising therapeutic strategy to restore vasodilator function in vascular disease. |
format | Online Article Text |
id | pubmed-6930636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69306362019-12-26 Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo Zaabalawi, Azziza Astley, Cai Renshall, Lewis Beards, Frances Lightfoot, Adam P. Degens, Hans Whitehead, Debra Alexander, Yvonne Harris, Lynda K Azzawi, May Molecules Communication The methylated analogue of the polyphenol resveratrol (RV), 2,3′,4,5′-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promising delivery modality for enhanced uptake into tissues. We examined the effect of delivery of TMS in liposomes on the restoration of vasodilator responses of isolated aortic vessels after acute tension elevation ex vivo. Aortic vessels from young male Wistar rats were isolated, and endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) responses assessed. Acute tension elevation (1 h) significantly reduced ACh dilator responses, which were restored following incubation with superoxide dismutase or apocynin (an NADPH oxidase inhibitor). Incubation with TMS-loaded liposomes (mean diameter 157 ± 6 nm; PDI 0.097) significantly improved the attenuated dilator responses following tension elevation, which was sustained over a longer period (4 h) when compared to TMS solution. Endothelial denudation or co-incubation with L-NNA (Nω-nitro-l-arginine; nitric oxide synthase inhibitor) resulted in loss of dilator function. Our findings suggest that TMS-loaded liposomes can restore attenuated endothelial-dependent dilator responses induced by an oxidative environment by reducing NADPH-oxidase-derived ROS and potentiating the release of the vasodilator nitric oxide. TMS-loaded liposomes may be a promising therapeutic strategy to restore vasodilator function in vascular disease. MDPI 2019-11-29 /pmc/articles/PMC6930636/ /pubmed/31795324 http://dx.doi.org/10.3390/molecules24234360 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Zaabalawi, Azziza Astley, Cai Renshall, Lewis Beards, Frances Lightfoot, Adam P. Degens, Hans Whitehead, Debra Alexander, Yvonne Harris, Lynda K Azzawi, May Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title | Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title_full | Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title_fullStr | Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title_full_unstemmed | Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title_short | Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo |
title_sort | tetramethoxystilbene-loaded liposomes restore reactive-oxygen-species-mediated attenuation of dilator responses in rat aortic vessels ex vivo |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930636/ https://www.ncbi.nlm.nih.gov/pubmed/31795324 http://dx.doi.org/10.3390/molecules24234360 |
work_keys_str_mv | AT zaabalawiazziza tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT astleycai tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT renshalllewis tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT beardsfrances tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT lightfootadamp tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT degenshans tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT whiteheaddebra tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT alexanderyvonne tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT harrislyndak tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo AT azzawimay tetramethoxystilbeneloadedliposomesrestorereactiveoxygenspeciesmediatedattenuationofdilatorresponsesinrataorticvesselsexvivo |