Biomedical Engineering Reference
In-Depth Information
released by the hydrolysis of the acetal groups and MDAwas produced
in the drinking water. Mice received 0.5%, 0.25%, or 0.125% (MDA) in
drinking water 6 days a week for life. Three methanol control groups
were also included in the study. Methanol (“controls”) was added to
water to create control solutions at levels that represented the stoichio-
metric amount of methanol liberated by the hydrolysis of the acetal
group in the different MA test groups. Six groups of 25 females and six
groups 25 males were used in this study (three treatment groups and
three methanol groups per sex). The mice were observed daily, weighed
weekly, and sacrificed when moribund. Complete autopsy were con-
ducted and section of skin, lung, liver, spleen, pancreas, kidney, adrenal
glands, esophagus, stomach, small and large intestine, rectum urinary
bladder, uterus, ovaries, or testes, prostate gland vesicular glands, and
any gross lesions, including tumors, were evaluated.
There was a treatment-related decrease in water consumption in the
MDA groups when compared to methanol control. The calculated
methanol daily dose in the MDA-treated groups ranged from
49.8mg in the top dose males to 15.3mg in the low dose females.
The top male treatment group actually received on average 28mg MDA
per day, while the low dose female received on average 8.6mg MDA per
day based on the reduced treated water intake. On the basis of a
calculated daily methanol dose in the MDA-treated group, the methanol
dose ranged from 450 to 2000mg/kg. Saturation of catalase, the enzyme
that biotransforms methanol to formaldehyde is reported to start at
about 600mg-methanol/kg bw in rats (Horton et al., 1992). Oxidative
damage is reported when catalase is saturated in rats (Skrzydlewska and
Farbiszewski, 1996, 1998; Skrzydlewska et al., 1998; Parthasarathy
et al., 2006; Dobrzynska et al., 1999). One of the products of this
oxidative damage is MDA. So it is possible that the MDA dose in the
mid and top MDA groups was actually higher than the calculated MDA
levels because of additional production of MDA as a result of lipid
peroxidation induced by methanol.
In the methanol control groups, the dose of methanol was much
higher than the actual dose in the respective MDA-treated animals
because of decreased water consumption in the MDA groups. The
calculated level of methanol ingested was 84.5/82.7mg in the high dose
