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Inhibition of P-glycoprotein transport: a mechanism for endocrine disruption in the channel catfish?
P-glycoprotein (pgp), an efflux transporter localized in a variety of tissues including the intestinal mucosa, renal tubules and bile canaliculi, is known to participate in the disposition of a variety of chemicals, including steroid hormones. This study examined the relationship of pgp to the movement into the bile of the hormone estradiol (E2), and the potential for transport interactions between the environmental pollutant nonylphenol ethoxylate (NPE) and E2. Biliary-cannulated in situ-prepared isolated perfused livers were used to assess pgp transport function. E2, in competitive transport preparations with Rhodamine 123 (Rho123), a pgp substrate, demonstrated significant decreases in Rho123 transport into bile, as did the prototypic inhibitor and substrate verapamil. [3H]E2 (0.28 nM) transport into bile was significantly reduced with either 20 M NPE or verapamil. These results suggest that E2 is a substrate and/or modulator for the catfish biliary pgp transporter, and that NPE potentially influences biliary transport and excretion of E2. 相似文献
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Our goal was to study the involvement of cytochrome P450 genes in estrogen metabolism and the extent to which the potentially carcinogenic 4-hydroxyestradiol metabolite is formed by channel catfish (Ictalurus punctatus; CC). Estradiol metabolism and ethoxyresorufin-O-deethylase (EROD) activity were assessed in several tissues from fish collected from three variably contaminated sites in the Mississippi River Delta, from laboratory control fish, and from fish exposed to 20 mg/kg benzo(a)pyrene (BaP) i.p. for 4 days. Liver EROD activity was induced by BaP, but Delta fish EROD activities were not statistically higher than activities in control fish. Gill microsomal EROD activity was also induced by BaP, but activities were 8- to 77-fold lower than those from liver. The predominant estrogen metabolites formed by CC liver, gill and gonad microsomes were 2-hydroxyestradiol and estrone as detected by GC/MS. Liver and gill 2-hydroxyestradiol formation was induced in BaP-dosed fish. The trends in hydroxyestradiol formation in field collected fish were more variable. In all fish liver microsomes there was more 2- compared to 4-hydroxyestradiol formed. However, BaP-treatment increased the 4:2 hydroxyestradiol ratio from 0.04 in control fish to 0.2 in BaP-exposed fish, suggesting that BaP induces the formation of the potentially genotoxic estrogen metabolite. No detectable 4-hydroxyestradiol was produced by gill and gonad microsomes. These results will ultimately help in determining which fish P450 genes are susceptible to environmental contamination and may be involved in estrogen genotoxicity. 相似文献
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Azevedo JS Braga ES Favaro DT Perretti AR Rezende CE Souza CM 《Marine pollution bulletin》2011,62(12):2724-2731
Santos-São Vicente estuary, located in São Paulo State, Brazil, has a history of contamination by inorganic chemicals such as mercury (Hg). In the 1980s the Cubatão was considered one of the most polluted sites in the world as a consequence of the intense industrial activities located in the city close to the estuary. To provide data and evaluate the local biota, total mercury (THg) contents were determined in sediments and in fish, Cathorops spixii, from different areas of the Santos-São Vicente estuary. For comparison, samples were also collected in a non-polluted system with similar hydrochemistry characteristics, the Cananeia estuary. The water characteristics and THg levels in sediment and fish samples confirmed a high human influence in the Santos-São Vicente estuary. The lowest THg values, observed in Cananeia, were evidence of low anthropogenic influence. High values observed in Santos-São Vicente show the necessity for a monitoring program. 相似文献
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