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Fernandes, Denise

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  • Drospirenone intake alters plasmatic steroid levels and cyp17a1 expression in gonads of juvenile sea bass
    Publication . Blanco, Maria; Fernandes, Denise; Medina, Paula; Blazquez, Mercedes; Porte, Cinta
    Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormone replacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigated in juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01-10 mu g DRO/g) for up to 31 days. DRO was detected in the blood (4-27 ng/mL) of fish exposed to the highest concentration, with no significant bioaccumulation over time and no alteration of hepatic metabolizing enzymes, namely, CYP1A and CYP3A-catalysed activities and UDP-glucuronyltransferase (UGT). Pregnenolone (P5), progesterone (P4), 17 alpha-hydroxyprogesterone (17P4), 17 alpha-hydroxypregnenolone (17P5), androstenedione (AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and cyp11 beta analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and AD detected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 in females evidence the ability of DRO to alter steroid synthesis at low intake concentrations (7 ng DRO/day). However, the potential consequences of this steroid shift for female reproduction remain to be investigated. (C) 2016 Elsevier Ltd. All rights reserved.
  • Mitochondrial metabolism of 17α-hydroxyprogesterone in male sea bass (Dicentrarchus labrax): a potential target for endocrine disruptors
    Publication . Fernandes, Denise; Bebianno, Maria João; Porte, Cinta
    The metabolism of 17alpha-hydroxyprogesterone (17P(4)) was investigated in different subcellular fractions isolated from male gonads of sea bass (Dicentrarchus labrax L). The existence of CYP17 (C17,20-lyase activity) and CYP11B (11beta-hydroxylase) catalyzed reactions was demonstrated in the mitochondrial fraction, where 17P(4) was converted to androstenedione (AD) and further metabolized to 11beta-hydroxyandrostenedione (betaAD). The synthesis of betaAD predominated in early spermatogenic testis, indicating a role of betaAD in testicular recrudescence. Additionally, the in vitro effect of model endocrine disrupting chemicals (i.e. nonylphenol (NP), p,p'-DDE, benzo[a]anthracene (BaA), tributyltin (TBT) and ketoconazole (KCZ)) on the mitochondrial metabolism of 17P(4) was investigated. Among the tested compounds, 100 microM NP inhibited the activity of CYP17 (C17,20-lyase) whereas 100 microM KCZ inhibited both CYP17 and CYP11B. Both chemicals showed the potential to disrupt the reproductive cycle of fish living in polluted environments due to impairment of testicular steroid biosynthesis. These results suggest that mitochondrial metabolism of 17P(4) may constitute a new sensitive probe for the assessment of endocrine disruption in fish.
  • Assessing pollutant exposure in cultured and wild sea bass (Dicentrarchus labrax) from the Iberian Peninsula
    Publication . Fernandes, Denise; Bebianno, Maria João; Porte, Cinta
    The aquaculture industry is an expanding activity, mainly due to the world population demand of fish. However, intensive production and the use of chemicals have raised environmental concerns and have questioned the quality of cultured fish in comparison to wild fish. Up to date, there is little information regarding pollutant residues in cultured stocks and the risks associated to consumption. Here we summarize recent data on pollutants exposure, together with biochemical responses in both cultured and wild sea bass (Dicentrarchus labrax) from the Iberian Peninsula. The obtained data highlights the use of chemicals in current aquaculture practices as a significant source of pollution in cultured fish that poses a risk to exposed individuals and may negatively impact aquatic ecosystems. Nonetheless, a controlled use of those chemicals and a careful selection of the aquaculture location can ensure relatively low and homogeneous levels of pollutants in cultured fish in comparison to wild specimens.