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The combination of glutamate receptor antagonist MK-801 with tamoxifen and its ...

Ribeiro, Mariana P. C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B. A.

Recent reports suggest that N-methyl-d-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As t...


The antiestrogen 4-hydroxytamoxifen protects against isotretinoin-induced perme...

Silva, Filomena S. G.; Ribeiro, Mariana P. C.; Santos, M. S.; Rocha-Pereira, Petronila; Santos-Silva, Alice; Custódio, José B. A.

The combination of isotretinoin (13-cis-retinoic acid) with antiestrogens seems to be a promising strategy for cancer chemotherapy. The aim of the study was to evaluate the effects of isotretinoin alone or in combination with 4-hydroxytamoxifen (OHTAM) and with its prodrug tamoxifen (TAM), on the functions of rat liver mitochondria, i.e., mitochondrial permeability transition (MPT), bioenergetic functions and a...


Comparative effects of three 1,4-dihydropyridine derivatives [OSI-1210, OSI-121...

Fernandes, Maria A. S.; Pereira, Susana P. S.; Jurado, Amália S.; Custódio, José B. A.; Santos, Maria S.; Moreno, António J. M.; Duburs, Gunars

The 1,4-dihydropyridines OSI-1210, OSI-1211 (etaftoron), and OSI-3802 are compounds with similar chemical structure. They differ by the length of the alkoxyl chain in positions 3 and 5 of the dihydropyridine (DHP) ring and by their pharmacological action characteristics. However, as far as we know, a clear relationship between the effects of these compounds and the length of the alkoxyl chain in positions 3 and...


Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-...

Moreira, Paula I.; Custódio, José B.A.; Nunes, Elsa; Moreno, António; Seiça, Raquel; Oliveira, Catarina R.; Santos, Maria S.

Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17[beta]-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated...


Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-...

Moreira, Paula I.; Custódio, José B.A.; Nunes, Elsa; Moreno, António; Seiça, Raquel; Oliveira, Catarina R.; Santos, Maria S.

Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17[beta]-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated...


Tetrandrine concentrations not affecting oxidative phosphorylation protect rat ...

Fernandes, Maria A. S.; Custódio, José B. A.; Santos, Maria S.; Moreno, António J. M.; Vicente, Joaquim A. F.

The effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca2+-induced opening ...


Brain mitochondrial injury induced by oxidative stress-related events is preven...

Moreira, Paula I.; Custódio, José B.; Oliveira, Catarina R.; Santos, Maria S.

This study evaluated the effect of the synthetic, nonsteroidal antiestrogen drug tamoxifen on the function of brain mitochondria. We observed that tamoxifen concentrations above 30 nmol/mg protein induced a slight decrease on RCR and ADP/O ratio. However, only higher concentrations of tamoxifen (>=70 nmol/mg protein) affected the phosphorylative capacity of mitochondria. Those effects were characterized by a de...


Hydroxytamoxifen protects against oxidative stress in brain mitochondria

Moreira, Paula I.; Custódio, José B.; Oliveira, Catarina R.; Santos, Maria S.

This study evaluated the effect of hydroxytamoxifen, the major active metabolite of tamoxifen (synthetic, nonsteroidal antiestrogen drug), on the function of brain mitochondria. We observed that only high concentrations of hydroxytamoxifen (60 nmol/mg protein) induced a significant decrease in RCR, while ADP/O ratio remained statistically unchanged. Similarly, only the highest concentration of hydroxytamoxifen ...


Protection of tamoxifen against oxidation of mitochondrial thiols and NAD(P)H u...

Cardoso, Carla M. P.; Almeida, Leonor M.; Custódio, José B. A.

The effects of tamoxifen (TAM) were studied on the mitochondrial permeability transition (MPT) induced by the prooxidant tert-butyl hydroperoxide (t-BuOOH) or the thiol cross-linker phenylarsine oxide (PhAsO), in the presence of Ca2+, in order to clarify the mechanisms involved in the MPT inhibition by this drug. The combination of Ca2+ with t-BuOOH or PhAsO induces mitochondrial swelling and depolarization of ...


Comparison of the changes in adenine nucleotides of rat liver mitochondria indu...

Cardoso, Carla M. P.; Moreno, António J. M.; Almeida, Leonor M.; Custódio, José B. A.

The antiestrogen tamoxifen (TAM) inhibits the growth of different estrogen receptor (ER)-negative cells. Recently, multiple effects of TAM on mitochondrial bioenergetic functions have been pointed to explain its ER-independent cell death mechanisms. We have shown that TAM and its major active metabolite 4-hydroxytamoxifen (OHTAM) induce depolarization of the mitochondrial membrane potential ([Delta][Psi]) and u...


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    Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia