Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative

Katalin Prokai-Tatrai, P. Perjési, Nilka M. Rivera-Portalatin, James W. Simpkins, Laszlo Prokai

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)280-288
Number of pages9
JournalSteroids
Volume73
Issue number3
DOIs
Publication statusPublished - Mar 2008

Fingerprint

Hydroquinones
Estrogens
Antioxidants
Derivatives
Estrogen Receptors
Hydroxyl Radical
Aromatization
Oxidative stress
Scavenging
Neuroprotective Agents
NAD
Lipid Peroxidation
Estradiol
Brain
Oxidative Stress
Hormones
Tissue
Lipids
Enzymes
17-butoxy-1,3,5(10)-estratrien-3-ol

Keywords

  • 17β-Butoxy-1,3,5(10)-estratrien-3-ol
  • Antioxidant neuroprotection
  • Chemical shield
  • Hydroxyl radical
  • Oxidative stress
  • Steroidal para-quinol

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. / Prokai-Tatrai, Katalin; Perjési, P.; Rivera-Portalatin, Nilka M.; Simpkins, James W.; Prokai, Laszlo.

In: Steroids, Vol. 73, No. 3, 03.2008, p. 280-288.

Research output: Contribution to journalArticle

Prokai-Tatrai, K, Perjési, P, Rivera-Portalatin, NM, Simpkins, JW & Prokai, L 2008, 'Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative', Steroids, vol. 73, no. 3, pp. 280-288. https://doi.org/10.1016/j.steroids.2007.10.011
Prokai-Tatrai, Katalin ; Perjési, P. ; Rivera-Portalatin, Nilka M. ; Simpkins, James W. ; Prokai, Laszlo. / Mechanistic investigations on the antioxidant action of a neuroprotective estrogen derivative. In: Steroids. 2008 ; Vol. 73, No. 3. pp. 280-288.
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