Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function
Document Type
Article
Publication Date
5-1-2017
Department
Department of Biological Sciences; Department of Chemistry
Abstract
Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.
Publication Title
Bioorganic and Medicinal Chemistry
Recommended Citation
Bi, W.,
Bi, Y.,
Gao, X.,
Li, P.,
Hou, S.,
Zhang, Y.,
Bammert, C.,
Jockusch, S.,
Legalley, T.,
Michael Gibson, K.,
&
Bi, L.
(2017).
Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function.
Bioorganic and Medicinal Chemistry,
25(9), 2545-2568.
http://doi.org/10.1016/j.bmc.2017.03.033
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/6052