Oleoyl-estrone metabolic effects in relation with caloric restriction in inbred beta rats with spontaneous obesity and type 2 diabetes

Rats endocriadas de la línea IIMBeta con obesidad, hipertriacilglicerolemia y diabetes espontáneas fueron tratadas con oleoil-estrona durante 10 días. Un grupo con restricción alimentaria fue incluido en el estudio a fin de aislar algunos efectos de la oleoil-estrona dependientes de la restricción calórica que ésta promueve. Veinticinco ratas Beta macho de 200 dias de edad a los que se suministró 0.2 ml de aceite de girasol por día se dividieron en los seguientes grupos: (1) dosis diaria de 10 nmol/g de oleoil-estrona ; (2) restringido; (3) control. Las variables medidas fueron: proteínas corporales totales, agua y lípidios; pesos de los panículos adiposos retroperitoneal y epididimario; urea, glucosa, insulina, colesterol y triacilgliceroles plasmáticos. Los valores de biomasa y de ingesta de alimentos se registraron diariamente. Los grupos tratados con oleoil-estrona y restringido mostraron variaciones similares en composicíon corporal y disminuciones significativas en peso corporal debidas a reducciones en la ingesta de alimentos. Los tratamientos con oleoil-estrona y restringido disminuyeron significamente los pesos de los panículos adiposos retroperitoneales, pero no de los epididimarios. En los grupos tratados con oleoil-estrona y restringido la hiperglicemia disminuyó y la insulinemia lo hizo en forma significativa. Los valores de colesterol total plasmático normal y la hipertriacilglicerolemia característicos de las ratas Beta disminuyeron fuertemente comparados con los controles, aunque alcanzaron valores significa-tivamente diferentes entre los grupos tratados con oleoil-estrona y restringido. El colesterol total plasmático aparece como más sensible a la restricción calórica que los traicilgliceroles a través de un efecto específico mediado por la oleoil-estrona.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Synthesis, estrogen receptor binding affinity and biological evaluation of some 2-thiazolylestrone and estratrieno [17,16-d] thiazole derivatives

Two series of 2-thiazolyestrone and estratrieno [17,16-d] thiazole derivatives have been designed and synthesized to study the effect of such heterocyclic rings, as modifications of estrone, on the receptor biding affinity, uterotrophic and antiimplantation activities. The key step in the synthesis involved regioselective 16-alpha bromination of 2-acetylestrone with cupric bromide avoiding 2-acetyl bromination. The other key intermediate 2-bromoacetylestrone was prepared by combined Friedel-Crafts reaction and Fries rearrangement of estrone with bromoacetyl chloride and aluminium chloride. The tested products were found to be relatively weak competitors at 0C for estrogen receptor. Uterotrophic and postcoital antifertility assays indicated variable effects relative to estradiol. Some products, particularly compounds IX and XI-XIII, induced significant increase [75-90%] in the rat uterine weight while compounds III, XI and XII displayed notable antiimplantation activity of 69-88% relative to that of estradiol. 2[2-p-chloroanilinothiazol-4-yl] estrone [XIII] had a significant agonist activity eliciting the highest uterotrophic activity [90%] while exhibiting a weak antiimplantation activity [32%]. The p-bromo XII and the p-tolyl XIV derivative imparted strong uterotrophic and antiimplantation activities