Pro-oxidant and antioxidant potential of catecholestrogens against ferrylmyoglobin-induced oxidative stress.
Ferryl heme proteins may play a major role in vivo under certain pathological conditions. Catecholestrogens, the estradiol-derived metabolites, can act either as antioxidants or pro-oxidants in iron-dependent systems. The aim of the present work was (1) to determine the effects of ferrylmyoglobin on hepatocyte cytotoxicity, and (2) to assess the pro/antioxidant potential of a series of estrogens (phenolic, catecholic and stilbene-derived) against ferrylmyoglobin induced lipid peroxidation in rat hepatocytes. Cells were exposed to metmyoglobin plus hydrogen peroxide to form ferrylmyoglobin in the presence of the transition metal chelator diethylentriaminepentaacetic acid. Results showed that ferrylmyoglobin induced an initial oxidative stress, mainly reflected in an early lipid peroxidation and further decrease in GSH and ATP. However, cells gradually adapted to this situation, by recovering the endogenous ATP and GSH levels at longer incubation times. Phenolic and stilbene-derived estrogens inhibited ferrylmyoglobin-induced lipid peroxidation to different degrees: diethylstilbestrol>estradiol>resveratrol. Catecholestrogens at concentrations higher than 1 microM also inhibited lipid peroxidation with similar efficacy. The ability of estrogens to reduce ferrylmyoglobin to metmyoglobin may account for their antioxidant activity. In contrast, physiological concentrations (100 pM-100 nM) of the catecholestrogens exerted pro-oxidant activities, 4-hydroxyestradiol being more potent than 2-hydroxyestradiol. The implications of these interactions should be considered in situations where local myoglobin or hemoglobin microbleeding takes place.
Department of Physiology, Medicine School, University of the Basque Country, 48080 Bilbao, Spain.
Rosa
R
Martínez
Kristina
K
Quintana
Rosaura
R
Navarro
César
C
Martín
M Luisa
ML
Hernández
Igor
I
Aurrekoetxea
José Ignacio
JI
Ruiz-Sanz
Mercedes
M
Lacort
M Begoña
MB
Ruiz-Larrea
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002393:Estrogens, Catechol / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008786:Metmyoglobin / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D000975:Antioxidants; D002393:Estrogens, Catechol; D017382:Reactive Oxygen Species; C028048:ferrylmyoglobin; D008786:Metmyoglobin