| Research Abstract |
Recently, it was generally demonstrated that activated neutrophils are responsible for the induction and development of inflammatory lesions accompanied with ischemia-reperfusion and several types of tissue damages, through the generation of hydroxyl radical and peroxynitrite from superoxide. The purpose of the present study is to prevent the generation of these substances via scavenging superoxide by anti-oxidant enzymes delivered to inflammatory lesions.
Activated leukocytes induce acute tissue damage, so that these cells may release reactive oxygen species including superoxide just after attachment to the endothelial cell-lining. To dismutate superoxide into oxygen molecule and hydrogen peroxide, at first, we synthesized a conjugate of superoxide dismutase (SOD) with polyethylene glycol (PEG; MW, 5 kDa), and a conjugate of nitroxyl spin probes, SOD mimics, with PEG. Secondly, we synthesized nitroxyl spin probes conjugated with hyaluronan, which is a legand against the hyaluronan receptor (CD 44) on the cell surface of inflammatory cells.
When these anti-oxidant substances, were subjected to the study for their in vivo behaviors, it was elucidated that these substances possess characters, remaining in the intravascular compartment and accumulating in the inflammatory lesion. Furthermore, we applied these substances to transient focal cerebral ischemia injury in mice. As a result, they significantly suppressed brain edema formation. Through these fact, the functional anti-oxidant polymers is thought to play a role in scavenging free radicals in inflammatory lesions.
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