TY - JOUR
T1 - Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative
AU - Prokai-Tatrai, Katalin
AU - Perjesi, Pal
AU - Rivera-Portalatin, Nilka M.
AU - Simpkins, James W.
AU - Prokai, Laszlo
N1 - Funding Information:
The authors wish to thank Dr. Evelyn J. Perez for completing the cell survival and receptor binding studies. This work was supported by the National Institute of Health Grants: NS44765 and RR12028. Laszlo Prokai is the Robert A. Welch Professor of the University of North Texas Health Science Center.
PY - 2008/3
Y1 - 2008/3
N2 - Antioxidant action is an important component of the complex neuroprotective effect of estrogens. Combining theoretical prediction and subsequent experimental confirmation by chemical and in vitro paradigms, this study focused on the mechanistic aspects of hydroxyl radical scavenging by 17β-butoxy-1,3,5(10)-estratrien-3-ol, a synthetic derivative of 17β-estradiol with increased potency to inhibit lipid peroxidation and reduced affinity to estrogen-receptors compared to the endogenous hormone. In the process that acts as a "chemical shield," the phenolic A-ring turns into 10β-hydroxy-17β-butoxy-1,3,5(10)-estratrien-3-one, a non-aromatic para-quinol, upon capturing hydroxyl radicals, which results in the complete loss of estrogen-receptor affinity and antioxidant activity. However, the parent compound is apparently recovered in brain tissue from this para-quinol via enzyme-catalyzed NAD(P)H-dependent reductive aromatization without causing oxidative stress. Taken together, our report argues for a previously unrecognized antioxidant cycle for estrogen-derived compounds.
AB - Antioxidant action is an important component of the complex neuroprotective effect of estrogens. Combining theoretical prediction and subsequent experimental confirmation by chemical and in vitro paradigms, this study focused on the mechanistic aspects of hydroxyl radical scavenging by 17β-butoxy-1,3,5(10)-estratrien-3-ol, a synthetic derivative of 17β-estradiol with increased potency to inhibit lipid peroxidation and reduced affinity to estrogen-receptors compared to the endogenous hormone. In the process that acts as a "chemical shield," the phenolic A-ring turns into 10β-hydroxy-17β-butoxy-1,3,5(10)-estratrien-3-one, a non-aromatic para-quinol, upon capturing hydroxyl radicals, which results in the complete loss of estrogen-receptor affinity and antioxidant activity. However, the parent compound is apparently recovered in brain tissue from this para-quinol via enzyme-catalyzed NAD(P)H-dependent reductive aromatization without causing oxidative stress. Taken together, our report argues for a previously unrecognized antioxidant cycle for estrogen-derived compounds.
KW - 17β-Butoxy-1,3,5(10)-estratrien-3-ol
KW - Antioxidant neuroprotection
KW - Chemical shield
KW - Hydroxyl radical
KW - Oxidative stress
KW - Steroidal para-quinol
UR - http://www.scopus.com/inward/record.url?scp=38649109472&partnerID=8YFLogxK
U2 - 10.1016/j.steroids.2007.10.011
DO - 10.1016/j.steroids.2007.10.011
M3 - Article
C2 - 18068745
AN - SCOPUS:38649109472
SN - 0039-128X
VL - 73
SP - 280
EP - 288
JO - Steroids
JF - Steroids
IS - 3
ER -