Biomedical Engineering Reference
In-Depth Information
tissue. Moreover, perhaps owing to a combination of subcellular
localization, packaging in nucleosomes, and repair mechanisms,
DNA is more resistant than lipids to MeOH-initiated oxidative damage
in adults.
7.5 CONCLUSIONS
Our results suggest the following:
As the metabolism of MeOH by rabbits is more similar than mice
to that in humans, the rabbit might be a more accurate model than
the mouse, and perhaps the rat, for predicting the human risk for
MeOH developmental toxicity.
Given that rabbits, which more closely reflect human MeOH
metabolism, and at least one strain of mice and one strain of rat,
are resistant to MeOH teratogenesis, it is questionable whether
the human risk for MeOH developmental toxicity can be accu-
rately assessed in sensitive rodent models.
The respectively enhanced and reduced susceptibility of aCat and
hCat mice to the embryopathic effects of MeOH in embryo
culture, albeit not in vivo, suggest that ROS may contribute to
the underlying mechanism of MeOH teratogenicity in rodents.
These results also suggest that embryonic catalase plays an
important protective role via its antioxidative activity, as distinct
from its peroxidative, MeOH-metabolizing role in maternal liver
or the embryo. The absence of modulation by altered catalase
expression in vivo merits further investigation.
The reduced embryopathies observed in MeOH-exposed mouse
embryos pretreated with a free radical spin trapping agent in
whole embryo culture further support a role of oxidative stress in
the mechanism of MeOH developmental toxicity.
MeOH appears to be less embryopathic than EtOH on a molar
basis, based on mouse embryo culture results, although it is
difficult to extrapolate this comparison to in vivo studies in
susceptible rodent strains where conditions are highly variable.
