Biomedical Engineering Reference
In-Depth Information
showing a small increase in MeOH peak plasma concentration and
AUC (Sweeting et al., 2010). The resistance of the C3H mice
in vivo is consistent with the lower susceptibility of this strain to
MeOH embryopathies in embryo culture compared to C57BL/6J
embryos. In the hCat mice, it is possible that the 1.5-fold increase
in embryonic catalase activity was insufficient to protect against
MeOH-initiated ROS formation, although the same hCat embryos
were protected in embryo culture. In light of the protective role
for embryonic catalase evident in embryo culture using these mice,
the in vivo resistance of the aCat strain to MeOH teratogenesis and
the nonsignificant protection in hCat mice may be due to con-
founding maternal factors other than hepatic metabolism, such as
placental transporters for MeOH and/or FA, or protective maternal
hormones.
In the catalase-modified mice, embryos were exposed in culture to
4mg/ml of EtOH (87mM) or 4mg/ml of MeOH (125mM). Although
these concentrations are not equimolar, it can be observed that a smaller
percentage of MeOH-exposed WT embryos closed their neuropore or
turned, despite the relatively higher molar concentration of MeOH,
while both EtOH- and MeOH-exposed WT embryos developed signifi-
cantly fewer somites than saline-exposed controls (Miller and Wells,
2011). These results suggest that the embryopathic molar potency of
MeOH is less than that for EtOH, and substantially so for some
developmental outcomes. Also interesting was that regardless of the
molar concentration, enhanced catalase significantly protected embryos
from several parameters that were affected by EtOH or MeOH, includ-
ing anterior neuropore closure, somite development, and turning
(Figures 7.23 and 7.24). This suggests that embryonic catalase activity
may be a potential risk factor for both EtOH and MeOH, and enhanced
embryonic catalase is protective.
7.4.3.2 Free Radical Spin Trapping Agent In embryo culture, MeOH-
exposed CD-1 mouse embryos pretreated with the free radical spin
trapping agent PBN exhibited reduced MeOH embryopathies, evi-
denced by increased anterior neuropore closure, turning, and somite
development, suggesting ROS involvement in the mechanism of MeOH
