Biomedical Engineering Reference
In-Depth Information
related alcohol EtOH (Dong et al., 2010). Additional potential mecha-
nisms, such as interference with the mitochondrial electron transport
chain, are yet to be investigated.
7.4.3 Teratogenicity of Methanol and Comparisons to Ethanol
7.4.3.1 Genetic Modulation of Catalase Genetically modified mice
with altered catalase activity were used to evaluate the role of catalase in
embryo culture, which removes potentially confounding maternal
factors, and in vivo. Mutant acatalasemic mice (aCat) with reduced
catalase activity were compared to their C3H WT controls, and
transgenic mice expressing human catalase (hCat) with enhanced
catalase activity were compared to their C57BL/6J WT controls (Miller
and Wells, 2011).
In embryo culture, MeOH was embryopathic in both the WT
C57BL/6J and C3H strains although the range and severity of embryo-
pathies were greater in the C57BL/6J strain (Miller and Wells, 2011).
hCat embryos with enhanced catalase activity were protected from
MeOH-initiated decreases in anterior neuropore closure, turning, and
somite development. In contrast, MeOH-exposed catalase-deficient
aCat embryos exhibited reduced anterior neuropore closure and head
length, whichwere not observed inMeOH-exposedWT controls (Figures
7.23 and 7.24). The respectively contrasting protection and increased
embryopathies in hCat and aCat embryos compared to their WT controls
suggest that ROS contribute to the mechanism of MeOH teratogenicity,
and that embryonic catalase, despite constituting only about 2-5% of
maternal activity, plays a developmentally protective role. This interpre-
tation is consistent with similar embryo culture and in vivo studies of the
ROS-initiating teratogen phenytoin (Abramov and Wells, 2011). The
results also suggest that the alternative peroxidative activity of catalase in
converting MeOH to formaldehyde, at least in embryonic tissues, does
not play a measurable role in modulating embryopathic risk.
In the same genetically modified mice, the effects of altered
catalase activity in the more complicated in vivo system were more
difficult to interpret. The C57BL/6J WT controls for the hCat dams
treated with MeOH (total dose of 4 g/kg i.p. on GD 8) had offspring
