19 Accumulation of Okadaic Acid and Detoxifying Enzymes in the Digestive. . .
221
involved in xenobiotic metabolism, steroids and lipid signalling synthesis, sterol
synthesis or the metabolism of desaturation or elongation of fatty acids, establishing
a microsomal electron transport sequence known as “mixed function oxidase
system”. The, oxidation-reduction reactions of this system allow hydroxylation of
multiple molecules and converts them into polar molecules in order to facilitate
their elimination (Guengerich 1988). The relationship between CPR and OA in
mussels is consistent with the involvement of some microsomal monooxygenases
in the metabolism of OA. Other authors have described similar results in hepatocyte
cultures from vertebrates (Tamaki et al. 2005; Guo et al. 2010).
The metabolites produced by the mixed function oxidase system are not easily
eliminated and are usually more toxic than the initial compounds. Such metabolites
can be conjugated with endogenous reduced glutathione to increase its polarity and
hence make it easier to eliminate them. GST catalyzes the conjugation of a variety of
endogenous and xenobiotic substrates with reduced glutathione (GSH) (Mannervik
1985; Listowsky et al. 1988). GST has an important role in preventing peroxidation
and detoxification of toxic substances. In this work we observed an increase of this
activity, parallel to decrease of OA and which was significantly correlated with CPR
activity (r: 0.516, 0.544 in males and females, respectively; p < 0.01) (Fig. 19.1b;
Table 19.1), suggesting its possible participation in OA metabolism.
The GST activity depends on the presence of reduced glutathione. The redox
balance of cellular glutathione is maintained by glutathione reductase (GR). This enzyme catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione
(GSH) (Ulusu and Tandogan 2007), which is also necessary for other enzymatic
activities, such as glutathione peroxidase and glyoxalase I. In our study, GR activity
showed a different behaviour in relation to OA accumulation, which was dependant
on the sex of the mussel. In males we observed an increase of GR activity at the
beginning of intoxication and then a decrease parallel to GST activity, when the OA
began decreasing. Thus our results show a significant correlation between GR and
GST activity (r: 0.498, p < 0.01) and between GR and OA accumulated (r: 0.483,
p < 0.01). In female mussels there are no notable differences with males, although
our results shows a GR activity inhibition at the beginning of the toxic episodes
(Fig. 19.1c), which is negatively correlated with OA accumulation (r: 0.514,
p < 0.01) (Table 19.1).
The oxidative reactions catalyzed by the mixed function oxidase system generate
large amounts of reactive species of O 2 and other molecules, such as ’ oxaldeydes,
which are highly toxic. Such molecules can be eliminated by the activity of other
enzymes concerned with oxidative defense. Some authors have also described the
induction by OA of these enzymes in vertebrate cell cultures (Fujii et al. 1994;
Matias et al. 1999) and mussels (Auriemma and Battistella 2004).
Among the other enzymes of oxidative defense, the glioxilases I and II catalyze
the coordinated detoxification of reactive ’ oxaldeydes with mutagenic and cytotoxic activity, converting them into their corresponding ’ -hydroxy acids (thiol ester
intermediaries) (Regoli et al. 1996).
The glioxalase I is also a GSH-dependent enzyme. ’ oxaldeydes and glutathione form spontaneously an intermediary hemithioaceatal, which is transformed
221
involved in xenobiotic metabolism, steroids and lipid signalling synthesis, sterol
synthesis or the metabolism of desaturation or elongation of fatty acids, establishing
a microsomal electron transport sequence known as “mixed function oxidase
system”. The, oxidation-reduction reactions of this system allow hydroxylation of
multiple molecules and converts them into polar molecules in order to facilitate
their elimination (Guengerich 1988). The relationship between CPR and OA in
mussels is consistent with the involvement of some microsomal monooxygenases
in the metabolism of OA. Other authors have described similar results in hepatocyte
cultures from vertebrates (Tamaki et al. 2005; Guo et al. 2010).
The metabolites produced by the mixed function oxidase system are not easily
eliminated and are usually more toxic than the initial compounds. Such metabolites
can be conjugated with endogenous reduced glutathione to increase its polarity and
hence make it easier to eliminate them. GST catalyzes the conjugation of a variety of
endogenous and xenobiotic substrates with reduced glutathione (GSH) (Mannervik
1985; Listowsky et al. 1988). GST has an important role in preventing peroxidation
and detoxification of toxic substances. In this work we observed an increase of this
activity, parallel to decrease of OA and which was significantly correlated with CPR
activity (r: 0.516, 0.544 in males and females, respectively; p < 0.01) (Fig. 19.1b;
Table 19.1), suggesting its possible participation in OA metabolism.
The GST activity depends on the presence of reduced glutathione. The redox
balance of cellular glutathione is maintained by glutathione reductase (GR). This enzyme catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione
(GSH) (Ulusu and Tandogan 2007), which is also necessary for other enzymatic
activities, such as glutathione peroxidase and glyoxalase I. In our study, GR activity
showed a different behaviour in relation to OA accumulation, which was dependant
on the sex of the mussel. In males we observed an increase of GR activity at the
beginning of intoxication and then a decrease parallel to GST activity, when the OA
began decreasing. Thus our results show a significant correlation between GR and
GST activity (r: 0.498, p < 0.01) and between GR and OA accumulated (r: 0.483,
p < 0.01). In female mussels there are no notable differences with males, although
our results shows a GR activity inhibition at the beginning of the toxic episodes
(Fig. 19.1c), which is negatively correlated with OA accumulation (r: 0.514,
p < 0.01) (Table 19.1).
The oxidative reactions catalyzed by the mixed function oxidase system generate
large amounts of reactive species of O 2 and other molecules, such as ’ oxaldeydes,
which are highly toxic. Such molecules can be eliminated by the activity of other
enzymes concerned with oxidative defense. Some authors have also described the
induction by OA of these enzymes in vertebrate cell cultures (Fujii et al. 1994;
Matias et al. 1999) and mussels (Auriemma and Battistella 2004).
Among the other enzymes of oxidative defense, the glioxilases I and II catalyze
the coordinated detoxification of reactive ’ oxaldeydes with mutagenic and cytotoxic activity, converting them into their corresponding ’ -hydroxy acids (thiol ester
intermediaries) (Regoli et al. 1996).
The glioxalase I is also a GSH-dependent enzyme. ’ oxaldeydes and glutathione form spontaneously an intermediary hemithioaceatal, which is transformed