Glucuronidation of Hydroxylated Polychlorinated Biphenyl by Channel Catfish Liver

챠넬메기 간에서 Hydroxylated Polychlorinated Biphenyl의 Glucuronidation

  • 신혜순 (덕성여자대학교 약학대학)
  • Published : 2008.09.30

Abstract

Hydroxylated polychlorinated biphenyl (OH-PCBs)는 PCB의 CYP-dependent oxidation의 대사물로서 잠재적 독성이 강하고 지질친화성을 가지며 생물군에 지속적인 축적성을 나타낸다. OH-PCBs의 해독화 효능을 조사하기 위하여 channel catfish 간에서 glucuronidation을 통한 해독작용 가능성을 평가하고 biphenyl 구조에 다양한 염소치환의 구조적 차이점에 따른 영향을 비교 분석하여 보았다. Kinetic parameters에서 $K_m$$V_{max}$$192{\sim}871{\mu}M$, $869{\sim}1774$ pmo1/min/mg으로써 4'-OH-PCB35와 4'-OH-PCB69이 가장 높은 속도의 glucuronidation을 나타냈으며, 구조적 차이점에서 phenolic group에 한 개의 염소치환이 존재할 경우보다 두 개의 염소치환이 존재할 경우에 OH-PCBs(p<0.001)의 glucuronidation에 대한 $V_{max}$를 현저하게 낮추는 결과를 보였다.

Keywords

References

  1. Barrie L, Gregor D, Hargrave B, Lake R, Muir D, Shearer R, Tracey B and Bidleman T. Arctic contaminants: sources, occurrence and pathways, Science of the Total Environment 1992; 122: 1-74 https://doi.org/10.1016/0048-9697(92)90245-N
  2. Bergman A, Klasson-Wehler E and Kuroki H. Selective retention of hydroxylated PCB metabolites in blood, Environmental Health Perspectives 1994; 102: 464-469 https://doi.org/10.2307/3432042
  3. Brouwer A and Van den Berg KJ. Binding of a metabolite of 3,4,3′,4′-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin, Toxicology and Applied Pharmacology 1986; 85: 301-312 https://doi.org/10.1016/0041-008X(86)90337-6
  4. Brouwer A, Morse DC, Lans MC, Schuur AG, Murk AJ, Klasson-Wehler E, Bergman A and Visser TJ. Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health, Toxicology and Industrial Health 1998; 14: 59-84 https://doi.org/10.1177/074823379801400107
  5. Connor K, Ramamoorthy K, Moore M, Mustain M, Chen I, Safe S, Zacharewski T, Gillesby B, Joyeux A and Balaguer P. Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships, Toxicology and Applied Pharmacology 1997; 14: 111-123
  6. Daidoji T, Gozu H, Iwano H, Inoue H and Yokota H. UDPglucuronosyyltransferase isoforms catalyzing glucuronidation of hydroxy-polychlorinated biphenyls in rat, Drug Metab Dispos 2005; 33: 1466-1476 https://doi.org/10.1124/dmd.105.004416
  7. Guvenius DM, Hassanzadeh P, Bergman Å, and Norén K. Metabolites of polychlorinated biphenyls in human liver and adipose tissue, Environ Toxicol Chem 2002; 21: 2264-2269 https://doi.org/10.1897/1551-5028(2002)021<2264:MOPBIH>2.0.CO;2
  8. Hovander L, Malmberg T, Athanasiadou M, Athanassiadis I, Rahm S, Bergman Å and Klasson-Wehler E. Identification of hydroxylated PCB metabolites and other phenolic halogenated pollutants in human blood plasma, Arch Environ Contam Toxicol 2002; 42: 105-117 https://doi.org/10.1007/s002440010298
  9. Iwata H, Tanabe S, Sakai N and Tatsukawa R. Distribution of persistent organochlorines in the oceanic air and surface seawater and the role of ocean on their global transport and fate, Environmental Science and Technology 1993; 27: 1080-1098 https://doi.org/10.1021/es00043a007
  10. James MO and Little PJ. Modification of benzo[a]pyrene metabolism in hepatic microsomes from untreated and induced rats by imidazole derivatives which inhibit monooxygenase activity and enhance epoxide hydrolase activity, Drug Metabolism and Disposition 1983; 11:350-354
  11. James MO, Tong Z, Rowland-Faux L, Venugopal CS, and Kleinow KM. Intestinal bioavailability and biotransformation of 3-hydroxy-benzo[a]pyrene in an isolated perfused preparation from channel catfish, Ictalurus punctatus, Drug Metabolism and Disposition 2001; 29: 721-728
  12. Kester MHA, Bulduk S, Tibboel D, Meinl W, Glatt H, Felany CN, Coughtrie MWH, Bergman A, Safe SH and Kuiper CGJM. Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs, Endocrinology 2000; 141: 1897-1900 https://doi.org/10.1210/en.141.5.1897
  13. Lehmler HJ and Robertson LW. Synthesis of hydroxylated PCB metabolites with the Suzuki-coupling, Chemosphere 2001, 45: 1119-1127 https://doi.org/10.1016/S0045-6535(01)00052-2
  14. Lowry OH, Roseborough NJ, Farr AL and Randall RJ. Protein measurement with the Folin phenol reagent, Journal of Biological Chemistry 1951; 193: 265-275
  15. Norstrom RJ and Muir DCG. Chlorinated hydrocarbon contaminants in arctic marine mammals, The Science of the Total Environment 1994; 154: 107-128 https://doi.org/10.1016/0048-9697(94)90082-5
  16. Sandau CD, Ayotte P, Dewailly E, Duffe J and Norstrom RJ. Pentachlorophenol and hydroxylated polychlorinated biphenyl metabolites in umbilical cord blood plasma of neonates from coastal populations in Quebec, Environ Health Perspect 2002; 110: 411-417 https://doi.org/10.1289/ehp.02110411
  17. Singh J and Wiebel FJ. A highly sensitive and rapid fluorometric assay for UDP-glucuronyl transferase using 3-hydroxybenzo[ a]pyrene as substrate, Analytical Biochemistry 1979; 98: 394-401 https://doi.org/10.1016/0003-2697(79)90158-1
  18. Tampal N, Lehmler H-J, Espandiari P, Malmberg T and Robertson LW. Glucuronidation of hydroxylated polychlorinated biphenyls (PCBs), Chem Res Toxicol 2002; 15: 1259-1266 https://doi.org/10.1021/tx0200212
  19. Van den Hurk P, Kubiczek GA, Lehmler H and James MO. Hydroxylated polychlor-inated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo [a]pyrene, Environmental Health Perspectives 2002; 110: 343-348 https://doi.org/10.1289/ehp.02110343
  20. Yoshimura T, Tanaka S and Horie T. Species difference and tissue distribution of uridine diphosphateglucuronosyltransferase activities towards E6080, 1-naphthol and 4-hydroxybiphenyl, J Pharmacobiodyn 1992; 15: 387-393 https://doi.org/10.1248/bpb1978.15.387