Quinolinedione유도체, OQ1과 OQ21에 의한 혈관 이완 억제에 Oxidative stress의 중요성

The Importance of Oxidative in the Inhibition of Vasorelaxation Induced by Quinolinedione Derivatives, OQ1 and OQ21

To reveal the inhibitory mechanism of NO-dependent vasorelaxation by quinone derivatives (OQ1 and OQ21), we have compared the generation of free radicals by oxidative stress and the formation of cellular adducts by arylation. First, we measured oxygen consumption by quinone derivatives as a marker of oxidative stress in order to investigate whether these quinone compounds could generate reactive oxygen species. Both OQ1 and OQ21 generated free radicals and OQ21 was more potent. These results suggsted that free radicals be involved in the inhibition of vasorelaxation by quinones. Next, we measured the binding capacity of quinone derivatives with intracellular GSH and protein thiols (-SH) in order to investigate whether these quinones have arylation capacity. Compared to positive control groups (menadione), both OQ1 and OQ21 depleted intracellular GSH and protein thiols very slightly. These compounds have low toxicities in mammalian tissues. From these results, we concluded that the inhibition of vasorelaxation by quinone derivatives (OQ1, OQ21) may be caused by generation of free radicals.