ABSTRACT
In the title chalcone derivative, C19H18O3, the cyclo-hexa-none ring adopts a distorted half-chair conformation and the dihedral angle between the aromatic rings is 52.20â (15)°. In the crystal, weak C-Hâ¯O hydrogen bonds link the mol-ecules into C(12) [001] chains.
ABSTRACT
Cadmium targets the vascular endothelium causing endothelial dysfunction and leakiness of endothelial barrier. Nitric oxide plays a major role in mediating endothelial functions including angiogenesis, migration and permeability. The present study investigates the nitric oxide effects on cadmium induced endothelial leakiness. Results of ex vivo and in vitro permeability assays showed that even a sub-lethal dose of cadmium chloride (1 µM) was sufficient to induce leakiness of endothelial cells. Cadmium drastically altered the actin polymerisation pattern and membrane tension of these cells compared to controls. Addition of nitric oxide donor Spermine NONOate (SP) significantly blunted cadmium-mediated effects and recover endothelial cells integrity. Cadmium-induced cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability and high reactive oxygen species generation. In brief, we show the protective role of nitric oxide against cadmium-mediated endothelial leakiness.
Subject(s)
Cadmium/toxicity , Cell Membrane Permeability/drug effects , Spermine/analogs & derivatives , Actins/metabolism , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Cyclic GMP/metabolism , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/pathology , Humans , Nitric Oxide Synthase Type III/metabolism , Reactive Oxygen Species/metabolism , Spermine/pharmacologyABSTRACT
Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities.