Tempol-Folate Conjugates to Prevent Oxidative Injury in Tissues

Application

Targeted anti-oxidative therapy for ischemia-reperfusion injury, hemorrhage, major surgery, kidney transplant, or acute renal failure.

Key Benefits

• Conjugation of Tempol with Folate does not alter the antioxidant property of Tempol.
• Tempol-Folate conjugates are more effective than Tempol alone at preserving kidney structure and function after ischemia-reperfusion injury.
• Conjugate enables the selective targeting of tissues, allowing a lower antioxidant dose, reducing possible side effects.

Technical Summary

Emory investigators have synthesized a novel tissue directed antioxidant to selectively target renal tissue, thereby preventing damage during ischemia-reperfusion injury. The antioxidant Tempol is a membrane-permeable superoxide dismutase mimetic that has shown beneficial effects in injured kidneys and other organs.

In mouse models of ischemia- reperfusion injury, Dr. Taylor's group has shown that Tempol-Folate conjugates are more effective at preventing oxidative damage in kidney cells than Tempol alone preserving renal structure and glomerular filtration. Additionally, this composition reduced inflammation and preserved tissue function as indicated by lower numbers of infiltrating macrophages and ameliorated markers of renal injury (superoxide levels, urinary albumin, plasma creatinine, blood urea nitrogen, etc).

The science of reperfusion injury is well understood, however no therapy, has proved effective in mediating the negative effects of reperfusion of ischemic cells. Historically, investigative treatments have shown limited outcomes. This composition offers a feasible option for mitigating the clinical manifestation of reperfusion injury.

Developmental Stage

Compositions have been successfully tested in vitro and in vivo animal studies.