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Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

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Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UK
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Division of Pharmacy and Optometry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
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Maternal and Fetal Health Research Centre, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9WL, UK
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Maternal and Fetal Health Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary’s Hospital, Manchester M13 9WL, UK
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Centre for Musculoskeletal Science and Sports Medicine, Faculty of Science and Engineering, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UK
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Institute of Sport Science and Innovations, Lithuanian Sports University, LT-44221 Kaunas, Lithuania
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Advances Materials and Surface Engineering Research Centre, Faculty of Science and Engineering, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UK
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Author to whom correspondence should be addressed.
Academic Editor: Marina A. Dobrovolskaia
Molecules 2019, 24(23), 4360; https://doi.org/10.3390/molecules24234360
Received: 19 October 2019 / Revised: 25 November 2019 / Accepted: 27 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue Cardiovascular Nanomedicines and Nanomaterials )
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. View Full-Text
Keywords: liposomes; 2,3′,4,5′-tetramethoxystilbene; endothelium; aorta; oxidative stress; reactive oxygen species; nitric oxide; vascular function liposomes; 2,3′,4,5′-tetramethoxystilbene; endothelium; aorta; oxidative stress; reactive oxygen species; nitric oxide; vascular function
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Zaabalawi, A.; Astley, C.; Renshall, L.; Beards, F.; Lightfoot, A.P.; Degens, H.; Whitehead, D.; Alexander, Y.; Harris, L.K.; Azzawi, M. Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo. Molecules 2019, 24, 4360.

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