Page 215 - The Toxicology of Fishes
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Biotransformation in Fishes                                                 195


                                           Exposure to metals, pyrollizidine alkaloids, pesticides,
                                                 peroxidized oils, toxic algae, fatty diet

                                                 Generation of reactive oxygen species
                                                       (O2  , H2O2, HO ) •
                                                         •—

                                        Lipid peroxidation
                                                                                 Liver
                                                              Protein and DNA   disease,
                                       Release toxic α, β        damage         mortality
                                       unsaturated aldehydes
                                       4 hydroxynonenal, 4HNE
                                                      H          GST,
                                                                 ADH       Detoxification
                                                       O
                                               O                 ALDH
                       FIGURE 4.13 Pathway for the generation and detoxification of 4-hydroxynonenal (4HNE). In mammals and certain fish
                       species, GST constitutes a protective pathway against 4HNE injury.


                       the prototypical xenobiotic substrates, with  ETHA being the highest.  GSTA1 has a fivefold higher
                       peroxidase activity (25 µmol/min/mg protein). The purified GSTA homolog of sea bass displays the same
                       characteristic profile of a high activity with N2E and relatively high activity with ETHA compared with
                       other substrates.
                        Largemouth bass (Micropterus salmoides) expresses a liver GST that shares extensive sequence
                       identity to the aforementioned 4HNE-metabolizing GSTA isolated from plaice that detoxifies 4HNE.
                       Interestingly, the bass GST exhibits a catalytic activity toward 4HNE that exceeds that of several
                       mammalian and aquatic species (Doi et al., 2004; Pham et al., 2002). Bass GSTA is also similar to a
                       GST form found in two other fish species (European flounder and fathead minnow); however, similar
                       genes may not be present in other aquatic species. Bass GSTA exhibits little sequence identity (21% or

                       TABLE 4.14
                       The Catalytic Properties of Glutathione S-Transferase in Cytosol and Glutathione Affinity-Column-Purified
                       Fractions from Several Fish Species
                                                                                       Activity
                                                                                  (nmol/min/mg protein)
                       Species               Preparation          Ref.          BPDE     EA     CDNB

                       Catfish            Liver cytosol     Gallagher et al. (1996)  5.3  37      1325
                        (Ictalurus punctatus)  Affinity purified fraction          128     —      24.000
                                         Intestinal cytosol  Gadagbui and James   8.3    65      1010
                                         Affinity purified fraction   (2000)       453     2880   107,000
                       Brown bullhead    Liver cytosol     Henson et al. (2001)  <5      —       1130
                        (Ameiurus nebulosus)  Affinity purified fraction           310     —       5,700
                       Rainbow trout     Liver cytosol     Melgar Riol et al. (2001)  —  20      630
                        (Oncorhynchus mykiss)  Affinity purified fraction          —       2030   77,180
                       Atlantic salmon   Liver cytosol     Novoa-Valinas et al. (2002)  —  70    290
                        (Salmo salar)    Affinity purified fraction                —       4350   16,600
                                         Kidney cytosol    Novoa-Valinas et al. (2002)  —  60    200
                                         Affinity purified fraction                —      10,620  37,500
                       Brown trout       Liver cytosol     Novoa-Valinas et al. (2002)  —  90    650
                        (Salmo trutta)   Affinity purified fraction                —       3790   27,690
                       Note: BPDE, (+)-anti-benzo(a)pyrene-7,8-dihydrodiol-9,10-oxide; EA, ethacrynic acid; CDNB, 1-chloro-2,4-dini-
                            trobenzene.
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