It is well known that exposure to excess levels of radiation leads to vascular contractile anomalies due to depression of the endothelium-dependent vasodilatation and increase of the vasoconstriction. These effects of radiation realized through in a large conductance Ca2+-activated K+ channels (BKCa) activity in vascular tissue. Both ’empty’ phosphatidilcholine liposomes (PCL) and free quercetin (Q) are known to repair radiation-induced vascular tone abnormalities, but Q is rather toxic and low soluble agent. So, the goal of this study was to compare effects of low toxic and high soluble phosphatidylcholine liposomes filled with quercetin (PCL-Q) and PCL, Q as well its simple mixture (PCL+Q) on functional activity of BKCa channels in rat thoracic aorta smooth muscle cells (SMCs) after ionizing irradiation. SMCs of thoracic aorta were obtained from anesthetized intact and irradiated (6 Gy) male Wistar rats (200-250 g) (100% survival rate (dose for LD50, 10 Gy)). The effects of whole body γ-irradiation (6 Gy) and quercetin-filled PCL on BKCa channels functional activity were studied using patch-clamp technique in whole-cell configuration. BKCa current density (paxilline-sensitive current) in control SMCs were 25±2 pA/pF at +70 mV (n=20). Ionizing irradiation decreased BKCa current density in SMCs to 13±1 pA/pF (n=15, P<0.05) and 5±1 pA/pF (n=17, P<0.05) on the 9th and 30th days, respectively. PCL-Q (3,4 µg/ml by quercetin and 124,0 μg/ml by lecithin), being added to the external solution, effectively increased BKCa current density in post-irradiated SMCs – to 24±3 pA/pF and 17±2 pA/pF (n=7, P<0.05) on the 9th and 30th days, respectively. The total effect PCL-Q appears to be the result of additive action of Q and PCL. The ratios of therapeutic effectiveness of PCL-Q, Q and PCL, being expressed quantitatively, may be presented as 1.0:0.6:0.4. The substances studied was without effect on the BKCa channels activity in control rat aorta SMCs. Experimentally obtained for PCL-Q and theoretically expected for Q+PCL dose-response curves demonstrate good coincidence. I/V curves obtained on the 9th and 30th days of post irradiation using simple mixture of PCL and Q in comparison with PCL-Q, confirm an additive effect PCL-Q constituents, i.e. the effects of PCL and Q simply summarize. The data obtained in this study clearly indicate that the ability of PCL-Q to restore BKCa channel activity damaged following irradiation can be realized due to additive action of liposomal form of lecithin itself and Q encapsulated into lipid vesicles. Encapsulation of flavonoids appears to be worthwhile therapeutic approach in case of ionizing irradiation accident as well in patients which underwent external radiotherapy.
University College Dublin (2009) Proc Physiol Soc 15, PC41
Poster Communications: Comparative study of quercetin-filled liposomes, free quercetin and ’empty’ liposomes regenerative effects on BKCa channels activity in rat aortic smooth muscles cells under ionized irradiation
S. Kyrychenko1, S. Tishkin1, A. Soloviev1
1. Department for Experimental Therapeutics, Institute of Pharmacology and Toxicology, Kiev, Ukraine.
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Where applicable, experiments conform with Society ethical requirements.