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1.
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   

2.
Several environmentally relevant contaminants are characterized as xenoestrogens by virtue of their ability to induce responses similar to 17β-estradiol (E2). There is concern that exposure to these xenoestrogens may result in endocrine and, thus, reproductive disruption. The objective of the present research was to determine whether xenobiotics known to elicit estrogenic responses in mammals were estrogenic in channel catfish, and if these compounds were capable of altering normal physiological response to E2. Sexually immature catfish were exposed by intraperitoneal injection to E2, suspected xenoestrogens or combination doses of E2 and xenoestrogen. Appearance of vitellogenin (Vg) in serum was used as the bioindicator of estrogenicity; Vg was measured by ELISA 7 days after injection. The ED50 of E2 for the appearance of Vg in blood, 0.6 mg/kg, was used as the positive control. Synthetic estrogens, ethinylestradiol, mestranol and DES were effective in inducing Vg; the antiestrogen tamoxifen inhibited response to E2 when given in a combination dose. Treatment by both methoxychlor and p-nonylphenol resulted in Vg appearance in serum; the doses required were 300 times that of E2, and the vitellogenic response was less when compared to the E2-induced response. In addition, a combination dose of methoxychlor with E2 decreased the magnitude of the response to E2. Other mammalian xenoestrogens, o,p′-DDT, chlordecone, lindane and β-HCH, were not able to produce a vitellogenic response in this study.  相似文献   

3.
Induction of hepatic cytochrome P450-dependent microsomal mono-oxygenase by xenobiotics is a well-established phenomenon in teleost fish. As in laboratory mammals, fish possess multiple forms of cytochrome P450 that display overlapping substrate specificity. One such isoform, CYP1A1, which has been cloned and sequenced from rainbow trout, has been shown to be orthologous to rat CYP1A1 and, as in mammals, is inducible up to several hundred-fold by planar aromatic hydrocarbons, PCBs and dioxins. It has been suggested that induction of CYP1A1 orthologues might provide a sensitive biomonitor for environmental pollution by mixtures of such compounds. In the current study, polyclonal antibodies directed against CYP1A1 purified from rat and trout liver were used to monitor induction of the CYP1A1 orthologue in hepatic microsomes from the fresh water species, the channel catfish (Ictalurus punctatus). Catfish from a local fish farm were induced in the laboratory by three daily injections of 50 mg/kg of the PCB mixture Aroclor 1254 and compared with fish taken from a site in central Arkansas—the Bayou Meto, known to be polluted with dioxin. Hepatic microsomal activities towards ethoxyresorufin (EROD) and pentoxyresorufin (PROD) were measured and Western blot analysis carried out with the two antibodies. EROD was elevated in both the Aroclor-treated fish and in the Bayou Meto fish compared with untreated fish farm controls; smaller but significant increases were observed in PROD. Spearman's rank correlations of 0·74 and 0·89 were observed between EROD and immunoquantified cross-reactivity towards the rat CYP1A1 and trout CYP1A1 antibodies.  相似文献   

4.
Previous studies have shown that aryl hydrocarbon receptor (AhR) agonists possess anti-estrogenic activities and several mechanisms have been proposed to explain the interactions between AhR and estrogen receptor (ER) signalling pathways. In the present study, we show that 3,3'4,4'5-pentachlorobiphenyl (PCB126 - a dioxin-like AhR agonist) produced estrogenic responses in the absence of ER agonist, in fish in vitro system. We exposed salmon primary hepatocytes to PCB126 (1, 10 and 50 pM) and the ER agonist nonylphenol (NP; 5 and 10 microM) singly and also in combination. Vitellogenin (Vtg) and zona radiata proteins (Zr-proteins) levels were analysed by semi-quantitative ELISA. We observed that the protein levels of Vtg and Zr-proteins were significantly induced in a concentration-specific manner in cells treated with PCB126 and NP, singly or in combination. In general, these results show a novel aspect of dioxin-like PCB effect not previously demonstrated in fish system.  相似文献   

5.
Polar bears bioaccumulate lipophilic pollutants, including polychlorinated biphenyls (PCBs), into their bodies from their exclusive diet of marine organisms. Hydroxylated PCB metabolites (OH-PCBs) have been found in plasma, presumably due to CYP-dependent biotransformation of PCBs in liver. Little is known about the phase 2 metabolism of hydroxylated xenobiotics in polar bears. The objective of this study was to examine UDP-glucuronosyltransferase (UGT) activity with OH-PCBs and a hydroxylated polycyclic aromatic hydrocarbon, 3-hydroxy-benzo(a)pyrene (3-OH-BaP), in polar bear liver. Samples of frozen polar bear liver were used to prepare microsomes. UGT activity with 3-OH-BaP in Brij-treated microsomes, measured by a fluorescence assay, was readily measurable with protein concentrations in assay tubes of up to 10 μg/ml, but dropped off very sharply at higher protein concentrations. The apparent Km for 3-OH-BaP was 1.71 ± 0.04 μM, and Vmax 1.26 ± 0.16 nmol/min/mg protein (mean ± SD, n=3). UGT activities with a model tetrachloro-OH-PCB (4′-OH-CB72) and a model hexachloro-OH-PCB (4′-OH-CB159) were assayed with [14-C]-UDPGA and separation of the [14-C]-glucuronide by ion-pair extraction and thin-layer chromatography. [14-C]-glucuronide conjugates were readily formed by polar bear liver microsomes in the absence of added substrate, apparently from contaminants present in liver. This phenomenon was not observed using hepatic microsomes from laboratory-held catfish. Glucuronidation efficiency was much higher with 4′-OH-CB72 (Km 7.3 μM; Vmax 1.55 nmol/min/mg) than 4′-OH-CB159 (Km 16.1 μM; Vmax 0.46 nmol/min/mg). The identities of the aglycones present in polar bear liver are not known, but could include OH-PCBs or hydroxylated metabolites of other persistent organic pollutants. This study demonstrates that UGT with high activity for 3-OH-BaP and other substrates is present in polar bear liver.  相似文献   

6.
Polar bears bioaccumulate lipophilic pollutants, including polychlorinated biphenyls (PCBs), into their bodies from their exclusive diet of marine organisms. Hydroxylated PCB metabolites (OH-PCBs) have been found in plasma, presumably due to CYP-dependent biotransformation of PCBs in liver. Little is known about the phase 2 metabolism of hydroxylated xenobiotics in polar bears. The objective of this study was to examine UDP-glucuronosyltransferase (UGT) activity with OH-PCBs and a hydroxylated polycyclic aromatic hydrocarbon, 3-hydroxy-benzo(a)pyrene (3-OH-BaP), in polar bear liver. Samples of frozen polar bear liver were used to prepare microsomes. UGT activity with 3-OH-BaP in Brij-treated microsomes, measured by a fluorescence assay, was readily measurable with protein concentrations in assay tubes of up to 10 g/ml, but dropped off very sharply at higher protein concentrations. The apparent Km for 3-OH-BaP was 1.71 +/- 0.04 microM, and Vmax 1.26 +/- 0.16 nmol/min/mg protein (mean +/- SD, n=3). UGT activities with a model tetrachloro-OH-PCB (4'-OH-CB72) and a model hexachloro-OH-PCB (4'-OH-CB159) were assayed with [14-C]-UDPGA and separation of the [14-C]-glucuronide by ion-pair extraction and thin-layer chromatography. [14-C]-glucuronide conjugates were readily formed by polar bear liver microsomes in the absence of added substrate, apparently from contaminants present in liver. This phenomenon was not observed using hepatic microsomes from laboratory-held catfish. Glucuronidation efficiency was much higher with 4'-OH-CB72 (Km 7.3 microM; Vmax 1.55 nmol/min/mg) than 4'-OH-CB159 (Km 16.1 microM; Vmax 0.46 nmol/min/mg). The identities of the aglycones present in polar bear liver are not known, but could include OH-PCBs or hydroxylated metabolites of other persistent organic pollutants. This study demonstrates that UGT with high activity for 3-OH-BaP and other substrates is present in polar bear liver.  相似文献   

7.
The carbamate pesticide, aldicarb, demonstrates significant acute toxicity in fish, and is readily biotransformed by most organisms studied. In fish, both the cytochrome P450 (CYP) and the flavin monooxygenase systems (FMO) are involved in bioactivating aldicarb to aldicarb sulfoxide, which is a more potent inhibitor of acetylcholinesterase (AChE). Channel catfish (Ictalurus punctatus), along with many other fresh water species, do not express FMO and are relatively resistant to the effects of aldicarb. This project examined the toxicity, AChE inhibition, metabolism, and toxicokinetic of aldicarb in channel catfish, and compared these values with an aldicarb-sensitive species, rainbow trout, which expresses FMO. Studies of in vitro and in vivo aldicarb biotransformation in catfish suggest that a low rate of bioactivation (10 times slower Vmax), resulting in less initial conversion to the activated metabolite, aldicarb sulfoxide, may be a contributing factor to resistance of channel catfish to aldicarb toxicity. These data are supported by toxicokinetic and enzyme inhibition studies. This work demonstrates that differences in FMO expression among fish species may have significant influence on toxicity resulting from exposure to some xenobiotics.  相似文献   

8.
The incidence of hepatoma, epidermal and other forms of cancerous growths in fish is well documented (Halver, 1967; Matsushima & Sugimura, 1976; Dawe et al., 1964). In fish, as in mammals, cancer may be a result of metabolically activated carcinogens. In mammals the primary enzyme system involved in the activation of environmental carcinogens is the cytochrome P-450 linked mixed-function oxidase (MFO). The hepatic microsomes of the species offish studied contain variable levels of cytochrome P-450. Liver microsomes of the trout Salmo trutta lacustris are surprisingly active in metabolising benzo-[a]pyrene (BP) and other compounds preferentially metabolised by polycyclic aromatic hydrocarbon (PAH)-specific cytochrome P-450. This finding may be significant, because it is apparent that the detrimental effects of PAHs require metabolic activation.We have studied the production of reactive intermediates of BP by following their binding to DNA and by measuring the specific nucleotide-BP metabolite complexes by chromatography. Untreated S. trutta liver microsomes catalyse the production of reactive intermediates of BP which bind to nucleotides of DNA at a rate that is 3–4 times higher than that catalysed by control rat liver microsomes. The most prominent DNA-BP metabolite adducts produced by trout liver microsomes are the nucleoside adduct of BP-7, 8-diol-9,10-epoxide and 9-OH-BP-4,5-oxide and other phenol oxides. In contrast to the trout, another fish species, roach (Rutilus rutilus), has extremely low activity. Although the in vitro binding of BP to DNA is not strictly correlated to in vivo binding or biological effects, our results show that reactive intermediates are formed by trout liver and thus the prerequisite for chemical carcinogenesis or mutagenesis is ful filled. This is further supported by the fact that in Ames's test, trout liver preparations produce mutagenic products from promutagens.  相似文献   

9.
Environmental chemicals may modulate the endocrine system through interaction with plasma sex steroid-binding proteins (SBP) and SBP-regulated processes. Some of these chemicals, which are known to interact with the estrogen receptor (ER), were found to bind competitively to the Atlantic salmon (Salmo salar) SBP and potentially disrupt the endocrine function of these proteins. Furthermore, both weakly acting (di-n-butyl phthalate) and potent estrogen mimics (ethynylestradiol), were able to induce a substantial up-regulation of circulating levels of SBP in vivo. Interestingly, modulation of SBP-levels was found to be a more sensitive endpoint than chemically induced interference with classical ER-mediated mechanisms for weakly acting estrogen mimics like di-(n-butyl) phthalate. Interference with the endocrine function of SBPs may thus introduce a novel mechanism for endocrine disruption, and give additional answers to the question why some weakly acting xenoestrogens are causing “estrogen-like” reproductive disturbances in developing males.  相似文献   

10.
A variety of anthropogenic chemicals are capable of binding to the estrogen receptor of vertebrate species. Binding of these compounds can interfere with homeostasis by disrupting normal gene expression patterns. The purpose of this study was to investigate the feasibility of applying array technology as a monitoring tool for detecting the presence and distribution of estrogenic compounds in coastal habitats using sheepshead minnows as our model. cDNA clones that were isolated from differential display, including vitellogenin alpha and beta, vitelline envelope protein (ZP2), and transferrin, among others, were spotted on the macroarray. The results of these experiments demonstrate a characteristic expression pattern of estrogen responsive genes in sheepshead minnows exposed to 17 beta-estradiol (E2).  相似文献   

11.
Benzo(a)pyrene (BaP) and polychlorinated biphenyls (PCBs) often co-exist in contaminated environments. Polychlorobiphenylols (OH-PCBs), formed by CYP-dependent monooxygenation of PCBs, are potent inhibitors of the glucuronidation of hydroxylated BaP metabolites. We hypothesized that OH-PCBs could drive the biotransformation of (−)BaP-7,8-dihydrodiol (BaP-7, 8-D) away from detoxication and towards formation of the reactive metabolite. A mixture of five OH-PCBs with 4–6 Cl atoms was infused into isolated, perfused, biliary intact livers (n=3 fish) removed from 3-methylcholanthrene-induced channel catfish. Controls (n=3) were infused with vehicle. Subsequently, [3H]-BaP-7, 8-D was infused into each liver and bile was collected for 1 h. The livers were taken for analysis of metabolites and DNA adducts. Induction status was confirmed by EROD assay. Bile was analyzed for metabolites. It was found that preinfusion of the mixture of OH-PCBs reduced the extent of glucuronidation of BaP-7, 8-D and increased the formation of DNA adducts 5-fold over controls. GSH conjugates, tetrols and triols were increased in the OH-PCB-infused fish, providing further support for our hypothesis that if the glucuronidation were inhibited, CYP-dependent activation would increase. These studies suggest a mechanism for synergy of toxicity of PAH and PCBs.  相似文献   

12.
The characteristics of steroid nuclear and membrane receptors and their interactions with xenobiotic chemicals in two marine perciform species, Atlantic croaker (Micropogonias undulatus) and spotted seatrout (Cynoscion nebulosus) are briefly reviewed. Several organochlorines that bind to the nuclear progesterone receptor in mammals show negligible binding to the nuclear progestogen receptor in seatrout ovaries. Two distinct nuclear androgen receptors with different tissue distributions have been identified in croaker, but only one of them binds xenobiotic anti-androgens previously identified in mammals. Multiple forms of the nuclear estrogen receptor (ER) have been identified in fishes. The ER in croaker testis has a higher affinity than the croaker liver ER for estrogens and xenoestrogens and may be more susceptible to chemical interference. In addition, differences in the feedback effects of estrogens and xenoestrogens on gonadotropin secretion in croaker are observed, depending on the stage of the reproductive cycle. Finally, the first clear evidence in any vertebrate for xenobiotic chemical interference with the nongenomic actions of steroids by binding to steroid membrane receptors was obtained with the seatrout ovarian progestogen membrane receptor and since has been confirmed with progestogen and estrogen membrane receptors in croaker sperm and testes. These various factors that influence chemical/steroid receptor interactions are likely to significantly modify steroid hormone actions at target tissues and consequently the toxicological effects of chemical exposure.  相似文献   

13.
To determine the estrogenicity of effluents from sewage treatment plants (STPs) to larval fish, 2-day-old sunshine bass were exposed to effluents from three STPs serving New York City (NYC), varying in size and treatment level. Estrogenic response was evaluated by measuring vitellogenin (VTG) and estrogen receptor (ER) expression in cytosolic fractions of whole body homogenates. Concentrations of the presumptive endocrine disruptors in the effluents were also measured. VTG and ER levels in sewage-exposed fish were 3-5 times that observed in controls. Combined concentrations of estradiol and estrone ranged from 5 to 13 ng/l and nonylphenol-ethoxylate metabolites (NPEOs: 4-nonylphenol, and 1-, 2-, and 3-nonylphenol-ethoxylates) ranged from 180 to 470 microg/l in chlorinated effluent. Results indicate that both ER and VTG can be used as biomarkers for endocrine disruption in larval fish, and that 4-day exposure to sewage effluent is sufficient to elicit significant expression of these markers in sunshine bass larvae. The extremely higher concentrations of NPEOs found in effluent relative to hormones (approximately 40,000-fold) indicates that surfactant metabolites may be contributing significantly to the estrogenic effects observed.  相似文献   

14.
Hepatic microsomes and cytosols of channel catfish (Ictalurus punctatus), rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), red tilapia (Oreochromis sp.), largemouth bass (Micropterus salmoides), striped bass (Morone saxatilis), hybrid striped bass (M. saxatilis × M. crysops), and bluegill (Lepomis macrochuris) (n = 8) were used to study the kinetics of phase I (ECOD, EROD, PROD, BROD) and phase II (UDP-glucuronosyltransferase (UDPGT)-, sulfotransferase (ST)- and glutathione-s-transferase (GST)-mediated) reactions. The best catalytic efficiency for ECOD and GST activities was performed by channel catfish, Atlantic salmon, rainbow trout and tilapia. The highest EROD catalytic efficiency was for Atlantic salmon. None of the species had either PROD or BROD activities. Rainbow trout had very similar UDPGT catalytic efficiency to tilapia, channel catfish, Atlantic salmon, largemouth bass and bluegill. Sulfotransferase conjugation had no significant differences among the species. In summary, tilapia, channel catfish, Atlantic salmon and rainbow trout had the best biotransforming capabilities; striped bass, hybrid striped bass and bluegill were low metabolizers and largemouth bass shared some capabilities with both groups.  相似文献   

15.
Lipid peroxidation, which is promoted in animal tissues by a variety of toxic agents, is believed to be associated with disruption of cell membranes and loss of activity of membrane-bound enzymes. While the process of lipid peroxidation has been well studied in mammals, only a few non-mammalian species have been examined.1 In the present study, in vitro assays for lipid peroxidation were performed using microsomes prepared from the livers of rats (Rattus rattus) and a marine fish, mullet (Mugil cephalus). Although lipid peroxidation was observed in microsomes prepared from both mullet and rat tissues, and was stimulated by xenobiotics, the mechanisms of generation appeared to be different. In contrast to rats, NADH was much more effective than NADPH in stimulating lipid peroxidation in mullet liver microsomes. The results suggest that NADH-dependent, as well as NADPH-dependent, lipid peroxidation may be important in vertebrate tissues.  相似文献   

16.
The metabolism of some xenobiotics can lead to the formation of reactive intermediates with mutagenic/carcinogenic properties. With the carcinogenic PAH these have been identified as bay-region diol-epoxides.1 Phenanthrene, a non-carcinogenic, bay-region containing model PAH, is metabolised in vivo by bony fish at the proximate bay-region position, whereas mammals and other marine organisms mainly form the K-region metabolite 9,10-dihydro-9,10-dihydroxy-phenanthrene.2 We wanted to investigate this difference more closely by studying the regiospecificity of phenanthrene metabolism in vitro both with microsomes from differently pretreated cod and with isolated cytochrome P-450 isozymes from BNF-induced cod.3 Secondly, by preparing antibodies to the major isozyme isolated (called cod P-450c), we investigated the immunochemical properties of the variously treated cod liver microsomes.  相似文献   

17.
Xenobiotic-mediated productions of reactive oxygen species, via enzymemediated redox cycling, have been implicated in a variety of toxicological phenomena including lipid peroxidation, enzyme inactivation and oxidative DNA damage leading to cancer. A comparison was undertaken of two benthic freshwater fish species that appear to differ markedly in their susceptibility to chemical carcinogenesis—the channel catfish (Ictalurus punctatus) and the more cancer-prone brown bullhead (Ameriurus nebulosus)-in terms of basic biochemical characteristics related to oxidative stress. This has included analysis of microsomal redox cycling of model xenobiotics (e.g. menadione) as well as antioxidant and other detoxifying enzymes in hepatic tissue of the two species. In addition, endpoints of oxidative stress, such as altered glutathione status and oxidative DNA damage, were examined. These studies have revealed numerous qualitative and quantitative differences between the two species both in terms of basal enzyme activities and in species response to model prooxidants. For example, bullhead appear to possess a greater capacity for microsomal redox cycling of xenobiotics, but have glutathione-dependent defense systems less able to withstand oxidative challenge. These and other interspecific differences have allowed for an improved understanding of the basic mechanisms which may underly species susceptibility to oxidative stress and critical manifestations such as cancer.  相似文献   

18.
Alterations to hepatic xenobiotic metabolizing enzymes (XMEs) is an important biomarker of contaminant exposure in aquatic toxicology. Measurement of XMEs in fish liver slices in vitro is an emerging tool for examining enzyme activity and response within the intact 3-D architecture of the liver tissue. We examined integrated phase I/phase II, and phase II metabolism of XMEs from liver slices in control and B[a]P-treated rainbow trout and channel catfish. Fluorescent assay substrates to measure rates of metabolism included 7-methoxycoumarin (7-MC), 7-ethoxycoumarin (7-EC) and 7-hydroxycoumarin (7-HC). Time-dependent increases in metabolism, and a lower rate of 7-MC metabolism compared with 7-EC metabolism, were observed at all time points for both fish species. In rainbow trout, B[a]P pretreatment caused a 10-fold increase in phase I metabolism of both 7-MC and 7-EC, and a 1.6-fold increase in phase II metabolism of 7-HC. Phase I activity in channel catfish was not notably altered by B[a]P pretreatment. However, B[a]P pretreatment in channel catfish caused a 48% decrease in phase II metabolism of 7-HC. These results indicate differences in baseline and B[a]P-altered XME profiles between rainbow trout and channel catfish.  相似文献   

19.
The effects of the mammalian inhibitor ellipticine (5,11-dimethyl-[6H]-pyrido[4,3b] carbazole) were examined in a mechanistic study of the cytochrome P450 monooxygenase system of control and β-naphthoflavone (βNF)-induced hepatic microsomes of Platichthys flesus. Ellipticine was indicated to bind to the haem moiety of cytochrome P450s (gave type II binding spectra) and to inhibit the transfer of electrons from both the hydrophobic binding site of cytochrome P450 reductase (P450R) to P450 (inhibited P450R reductase activity) and the hydrophilic binding site of P450R to soluble electron acceptors (inhibited NAD(P)H-cytochrome c reductase activity). No effect was seen on cytochrome b5 reductase activity. Ellipticine inhibition indicated the involvement of (i) P450R (possibly also P450s) in NADPH- but not NADH- dependent hydroxyl radical production, and (ii) electron transfer and P450/P450R interaction in NADPH-dependent cytochrome P450 1A-catalysed monooxygenation (7-ethoxyresorufin O-deethylase activity and benzo(a)pyrene (BaP) metabolism). Differential effects of ellipticine on cumene hydroperoxide (CHP)-dependent BaP metabolism (P450 peroxidase activity) with CHP concentration indicated the existence of at least two forms of P450 with different substrate affinities for CHP, and different mechanisms of formation for protein adducts and free metabolites. Overall, the studies indicate the primary site of action of ellipticine in P. flesus is binding between Fe3+-P450 and P450R.  相似文献   

20.
The effects of waterborne nitrite (3 mg/l NO2) on channel catfish were studied to evaluate changes in hematological parameters and phase I–II biotransformation in liver slices. Nitrite-exposed fish had significantly higher methemoglobin, blood and liver nitrite, and significantly lower pO2 than control fish. Total phase I-mediated metabolism of 7-ethoxycoumarin (EC) was not altered in nitrite-exposed fish compared with control fish (291±43 and 312±20 pmol/mg/h, respectively). However, phase II glucuronosyltransferase-mediated metabolism of 7-hydroxycoumarin (HC), both as a phase I metabolite of EC and as a parent substrate, was elevated in nitrite-exposed fish (204±17 and 1007±103 pmol/mg/h, respectively) as compared to control fish (149±14 and 735±87 pmol/mg/h) (P<0.05). Sulfotransferase-mediated metabolism of HC (as a metabolite of EC and as a parent substrate) was not notably altered in nitrite-exposed fish (95±16 and 617±33 pmol/mg protein/h, respectively) as compared with control fish (118±24 and 575±55 pmol/mg/h, respectively). These studies indicate that in vivo nitrite exposure and associated changes in hematological parameters do not appear to affect hepatic phase I EC biotransformation in channel catfish. However, subtle but significant changes in phase II glucuronidation, but not sulfation activity, were observed. The mechanism of these alterations is unclear. However, the data suggest that environmentally realistic concentrations of nitrite may affect the dynamics of conjugative metabolism in exposed fish.  相似文献   

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