Quercetin-filled phosphatidylcholine liposomes restore abnormalities in rat thoracic aorta BKCa channel function following iomzing irradiation

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SOLOVIEV Anatoly(Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev 03057, Ukraine)
TISHKIN Sergey(Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev 03057, Ukraine)
KYRYCHENKO Sergey(Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev 03057, Ukraine)
Journal Title:
Volume 61, Issue 03, 2009
Key Word:
smooth muscle;radiation;reactive oxygen species;potassium channels;quercetin;liposomes;protein kinase C

Abstract: The goal of the present study was to investigate the effects of quercetin-filled phosphatidylcholine fiposomes (PCL-Q) on the currents carried by large conductance CaCa-dependent K+ channels (BKCa) in rat thoracic aorta following non-fatal whole-body ionizing irradiation. Using patch-clamp technique, it is found that the outward K+ currents of isolated smooth muscle cells (SMCs)stimulated by depolarizing voltage steps were sensitive to BKCa inhibitor, paxilline, and this kind of outward K+ currents in SMCs from irradiated animals demonstrated a significant decrease in amplitude. Radiation-induced BKCa suppression was evident 9 days post-irradiation and progressively increased over 30 days of experimental period. Thus, the vasorelaxing force of these SMCs may be diminished following irradiation. PCL-Q effectively restored BKCa function in post-irradiated SMCs. It is noteworthy that the constituents of PCL-Q, i.e., free quercetin (Q) and "empty" liposomes (PCL), being taken separately, showed a decreased ability to recover BKCa function as compared with combined composition. These results suggest that PCL-Q is able to regain normal function of BKCa following irradiation. The protective effects of PCL-Q can be explained by its antioxidant and membrane repairing properties as well as its ability to inhibit protein kinase C activity. Thus, the lipid encapsulation of flavonoid, PCL-Q, appears to be a potential medication in the case of ionizing irradiation accident, and for the patients with neoplasm who have to receive external radiotherapy as well.

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