Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0271276 (Hudson)
 1,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochromes P450 (CYP, phase I) and conjugating (phase II) enzymes can be induced by and influence the toxicokinetics (metabolism) and toxicity of xenobiotic contaminants in exposed organisms. Beluga whale (Delphinapterus leucas) from the endangered St. Lawrence (SL) River Estuary population exhibit deleterious health effects and various severe pathologies that have been associated with contaminant exposure. In contrast, such effects (e.g. reproductive and immunological impairment) are generally less frequent in less exposed populations in the Canadian Arctic (CA). In the present study, opportunistic sampling resulted in the collection immediately after death of liver tissue from a single female neonate SL beluga (SL6) and male and female CA beluga (n=10) from the Arviat region of western Hudson Bay, in addition to sampling of stranded carcasses of male and female SL beluga (n=5) at least 12 h postmortem. We immunologically characterized cross-reactive proteins of hepatic microsomal CYP1A, CYP2B, CYP3A, CYP2E, epoxide hydrolase (EH) and uridine diphosphoglucuronosyl transferase (UDPGT) isozymes. Cross-reactive proteins were found in all SL and CA beluga using anti-rat CYP1A1, anti-rainbow trout CYP3A, anti-human CYP2E1, anti-rabbit EH and anti-human UDPGT1A1 polyclonal antibodies (Abs), whereas faintly cross-reactive CYP2B proteins were only found in SL6 and the CA samples using an anti-rabbit CYP2B1 Ab. In corresponding catalytic activity assessments, only SL6 and all CA beluga microsomal samples exhibited CYP1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activity (51-260 pmol/mg/min), CYP3A-mediated activity (113-899 pmol/mg/min) based on the formation of 6beta-hydroxytestosterone using a testosterone hydroxylase assay, and UDPGT activity (830-4956 pmol/mg/min) based on 1-naphthylglucuronide formation. The marginal cross-reactivity with the anti-CYP2B1 Ab and lack of catalytically measurable hydroxytestosterone isomers associated with CYP2B-type activity in all the SL and CA animals is suggestive of low CYP2B-type enzyme expression in beluga. The absence of measurable total P450 enzyme levels and catalytic activities in samples from the stranded SL belugas suggested catalytically inactive enzymes as a consequence of tissue degradation related due to the time delay of sample collection after death. However, all SL and CA animals demonstrated similar, immunologically cross-reactive phase I and II hepatic enzyme profiles, which is suggestive of the importance of metabolism in the toxicokinetics and fate of xenobiotics in animals from both populations
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PMID:Characterization and profiling of hepatic cytochromes P450 and phase II xenobiotic-metabolizing enzymes in beluga whales (Delphinapterus leucas) from the St. Lawrence River Estuary and the Canadian Arctic. 1521 Feb 96

Although polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDE) flame retardants are important organic contaminants in the tissues of marine mammals, including those species from the Arctic, there is exceedingly little direct evidence on congener-specific biotransformation. We determined and compared the in vitro metabolism of environmentally relevant PCB (4,4'-di-CB15, 2,3',5-tri-CB26, 2,4,5-tri-CB31, 2,2',5,5'-tetra-CB52, 3,3',4,4'-tetra-CB77, 2,2',4,5,5'-penta-CB101, 2,3,3',4,4'-penta-CB105 and 2,3',4,4',5-penta-CB118), and PBDE (4,4'-di-BDE15, 2,4,4'-tri-BDE28, 2,2',4,4'-tetra-BDE47, 2,2',4,5'-tetra-BDE49, 2,2',4,4',5-penta-BDE99, 2,2',4,4',6-penta-BDE100, 2,2',4,4',5,5'-hexa-BDE153, 2,2',4,4',5,6'-hexa-BDE154 and 2,2',3,4,4',5',6-hepta-BDE183) congeners using hepatic microsomes of a beluga whale (Delphinapterus leucas) from the Arviat (western Hudson Bay) area of the Canadian Arctic. Ortho-meta bromine-unsubstituted BDE15, BDE28 and BDE47 were significantly metabolized (100%, 11% and 5% depleted, respectively) by beluga, whereas control rat microsomes (from pooled male Wistar Han rats) metabolized BDE28, BDE49, BDE99 and BDE154 (13%, 44%, 11% and 17% depleted, respectively). CB15 and CB77 (putative CYP1A substrates) were more rapidly metabolized (100% and 93% depleted, respectively) by male beluga than CB26 and CB31 (CYP1A/CYP2B-like) (25% and 29% depleted, respectively), which were more rapidly metabolized than CB52 (CYP2B-like) (13% depleted). Higher chlorinated CB101 and CB105 showed no depletion. Rat control microsomes metabolized CB15 to a lesser extent (32% depleted) than beluga, but much more rapidly transformed CB52 (51% depleted, respectively). Within the 90 min in vitro assay time frame, the preference was towards metabolism of ortho-meta unsubstituted congeners (for both PCBs and PBDEs) in beluga whale, whereas for rat controls, meta-para unsubstituted congeners also substantially metabolized. For both beluga whale and rat, metabolic rates were inversely associated with the degree of halogenation. For the rapidly biotransformed CB15 and BDE15, water-soluble OH-metabolites were detected after incubation. These results indicate that CYP-mediated oxidative hepatic biotransformation is a metabolic pathway in the toxicokinetics of both PCB and PBDE congeners in beluga whales and in the rat model. This may suggest that the formation of potentially toxic oxidative PCB and PBDE products (metabolites), in addition to the parent pollutants, may be contributing to contaminant-related stress effects on the health of beluga whale.
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PMID:Biotransformation of polybrominated diphenyl ethers and polychlorinated biphenyls in beluga whale (Delphinapterus leucas) and rat mammalian model using an in vitro hepatic microsomal assay. 1632 35