Page 207 - The Toxicology of Fishes

Biotransformation in Fishes 187

TABLE 4.8
Compounds Glucuronidated in Fish
Chemical Class Examples
Aromatic hydrocarbons Benzene (metabolite phenol)
Naphthalene (metabolite 1-naphthol)
Aliphatic hydrocarbons Hexachlorocyclohexane (lindane)
Polyaromatic hydrocarbons (phenol Phenanthrene, pyrene, chrysene, benzo(a)pyrene, retene (7-isopropyl-
and diol metabolites) 1-methylphenanthrene)
N-Heteroaromatics Quinoline, dimethylquinoline, carbazole
Aromatic amines Aniline, 2,4-dichloroaniline, naphthylamine
Thioazole 2-Amino-4-phenylthiazole (anesthetics, such as Piscaine™; the
N-glucuronide)
O-Heteroaromatics (hydroxylated or Dibenzofuran(s), tetrachlorodibenzofuran, 7-ethoxycoumarin
dealkylated metabolites)
S-Heteroaromatics Dibenzothiophene
Biphenyls (hydroxylated metabolites) Biphenyl, tetrachlorobiphenyl
Resin acids Abietic, hehydroabietic, hydroabietic, isopimaric, pimaric acids (present in
wood pulps)
Phenolics Phenol 1-naphthol, 4-amino phenol, 1-chlorophenol, penta-chlorophenol
(wood preservatives), chlorophenolics formed during paper bleaching,
4-nitrophenol, 3-trifluoromethylnitrophenol (lampreycide),
phenolphthalein, phenolsulfonphthalein (dyes, slow), aflatoxicol M
(aflatoxin B 1 metabolite)
Phenolic xenoestrogens Bisphenol A, diethylstilbesterol, 4-nonylphenol, nonylphenol diethoxylate,
tert-octylphenol (degradation products of alkylphenoxylate detergents)
Phytoestrogens Coumesterol, genistein, biochinin A
Antibiotics Chloramphenicol, oxolinic acid, dimethylquinoline, miloxacin
Insecticides Organophosphates (e.g., fenitrothion malathion, chloropyriphos);
carbamates (e.g., 1-naphthyl-N-methylcarbamate, Sevin™); pyrethroids
(e.g., pyrethrin)
Fungicides Imidazole (e.g., Prochloraz™), pentachlorophenol
Plasticizers mono-Ethylhexylphthalate, di-2-ethylhexylphthalate
Miscellaneous industrial chemicals, drugs Picric acid, picramic acids, morphine, valproic acid, pristane, digoxigenin
monodigitoxide
Endobiotics Bilirubin, bilirubin glucuronide; cholic acids, cholate, deoxycholate,
lithocholate; retinoic acid; triodothyronine (T3), thyroxine (T4);
3α-hydroxysteroids (androsterone); 3-hydroxysteroids (estradiol,
estrone); 17β-hydroxysteroids (testosterone, 17-methyltestosterone)

glucuronidation in isolated microsomal preparations from fish. The liver is the most active tissue (see
later section). Planar phenols such as 4-nitrophenol, 1-naphthol, and 4-methylumbelliferone are readily
conjugated, although the rate may vary by as much as an order of magnitude between species. One
difficulty in intercomparison is the well-known latency observed in microsomes due to the lumenal
orientation of the enzyme and inaccessibility of UDPGA. In fish, this latency, which varies in a tissue-
specific manner, does not appear to be so great as in mammals. Maximal activity in microsomes is only
obtained in the presence of an optimized amount of detergent; indeed, an excess of detergent has an
inhibitory effect (Burchell and Coughtrie, 1989; Clarke et al., 1992b). Many published results are not
comparable because the species differences are remarkable, most notable being the much lower capacity
for conjugation of phenols in trout than plaice (George, 1994).

Enzymology of Piscine UGTs
The UGTs are membrane-bound enzymes that are quite labile when isolated, requiring phospholipids
to maintain activity; therefore, UGTs have proven to be notoriously difficult to purify and characterize.
The only non-mammalian UGTs to be purified were from the plaice (Clarke et al., 1992c). At least six
immunoreactive UGT peptides were visualized in plaice microsomes in western blots with mammalian