Biomedical Engineering Reference
In-Depth Information
blot analysis confirmed a higher expression of GAP-43 in the 2% and
4% methanol-exposed FAD rats.
The Aziz et al. (2002) study provides evidence that hepatic tetrahy-
drofolate is an important factor in methanol-induced developmental
neurotoxicity in rodents. The effects of methanol (increased spontane-
ous locomotor activity, decreased CAR, disturbances in dopaminergic
and cholinergic receptors, and increased expression of GAP-43 in the
hippocampal region) were more pronounced in FAD as compared to
FAS rats. Thus, alterations in available folic acid, particularly to the
conceptus, could have significant impacts on the developing fetus apart
from the influence it is presumed to have on formate removal. These
results do not implicate any particular proximate teratogen, as folate
deficiency can increase levels of methanol, formaldehyde and formate
(Medinsky et al., 1997). The immature blood-brain barrier and an
inefficient drug-metabolizing enzyme system make the developing
brain a sensitive target organ for the effects of methanol.
5.3.7 Role of Methanol and Metabolites in the Developmental
Toxicity of Methanol
Andrews et al. (1993a) examined the direct toxicity of methanol to
CD-1 mouse and Sprague-Dawley rat embryos developing in culture. In
rat embryos, methanol concentrations of 8mg/ml culture medium and
above resulted in decreased growth and development, and 12mg/ml
resulted in dysmorphogenesis in 66% of live embryos as well as 53%
embryo mortality. In comparison, methanol concentrations of 4mg/ml
culture medium affected growth and development of mouse embryos,
and dysmorphogenesis was observed in 58% of embryos cultured in the
presence of 6mg/ml. Importantly, in both the rat and the mouse,
concentrations of methanol required to cause developmental toxicity
in vitro were similar to peak maternal blood levels following develop-
mentally toxic exposures in vivo (rats, Nelson et al., 1985; mice, Rogers
et al., 1993). Brown-Woodman et al. (1995) reported similar findings
for the effects of methanol on Sprague-Dawley rat embryos in culture,
with concentrations of 286.5
mol/ml (9.17mg/ml) being developmen-
tally toxic. These results demonstrated that methanol does not require
m