Quercetin-filled phosphatidylcholine liposomes restore abnormalities in rat thoracic aorta BK(Ca) channel function following ionizing irradiation.
The goal of the present study was to investigate the effects of quercetin-filled phosphatidylcholine liposomes (PCL-Q) on the currents carried by large conductance Ca(2+)-dependent K(+) channels (BK(Ca)) 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 BK(Ca) inhibitor, paxilline, and this kind of outward K(+) currents in SMCs from irradiated animals demonstrated a significant decrease in amplitude. Radiation-induced BK(Ca) 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 BK(Ca) 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 BK(Ca) function as compared with combined composition. These results suggest that PCL-Q is able to regain normal function of BK(Ca) 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.
Soloviev
Anatoly
A
Institute of Pharmacology and Toxicology, Academy of Medical Science, Kiev, Ukraine. tonysolpharm@ukrpost.ua
Tishkin
Sergey
S
Kyrychenko
Sergey
S
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000528:radiation effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008081:Liposomes / Q000737:chemistry*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018408:Patch-Clamp Techniques; D010713:Phosphatidylcholines / Q000737:chemistry*; D011794:Quercetin / Q000494:pharmacology*; D011839:Radiation, Ionizing; D051381:Rats
D051036:Large-Conductance Calcium-Activated Potassium Channels; D008081:Liposomes; D010713:Phosphatidylcholines; D011794:Quercetin