Biomedical Engineering Reference
In-Depth Information
In rats, the oxidation of methanol is provided mainly by catalase (not
alcohol dehydrogenase, the primary enzyme in oxidation of alcohols in
humans). In humans, catalase is not involved in the metabolism of
methanol to formaldehyde and ROS and lipid peroxidation following
methanol exposure have not been reported in humans.
Catalase, which is found widely in the rodent tissues, normally
provides protection by attacking and detoxifying superoxide radicals
such as hydrogen peroxide (Parthasarathy et al., 2006). High doses of
methanol saturated the catalase enzyme in rodents (600-1000mg/kg
bw) (Horton et al., 1992) and the blood methanol level increases
dramatically as does ROS and lipid peroxidation, which are indicator
of oxidative damage. Because methanol is water soluble, it is found
throughout the rodent body at doses above saturation of the enzyme
catalase. This results in the possibility of lipid peroxidation and ROS in
various tissues and organs.
Methanol and oxidative stress has been studied in several short-term
studies in rodents, rabbits, and primate. These rat studies are described
in greater detail in this topic in Chapter 4, while recent studies of
methanol and oxidative stress in mice, rabbit, and primates are
described in greater detail in Chapter 7. Oxidative stress is seen
when the antioxidant capability of the target cell becomes insufficient
to prevent the increased formations of ROS. The antioxidant status was
evaluated by the increase in lipid peroxidation (thiobarbituric acid
reacting substances (TBA)), MDA, and enzymatic changes (superoxide
dismutase (SOD), Glutathione peroxidase (GSH-Px), glutathione
reductase (GSsG-R), catalase (CAT), and effects on nonenzymatic
antioxidants (ascorbate,
a
-topcopherol, nonprotein- and protein-bound
sulfhydryl compounds).
There are several oral short-term studies in rats receiving high doses
of methanol (1.5, 3, or 6 g/kg bw which is greater than the level where
catalase is saturated) receiving methanol by gavage and were scarified
at different time periods from 6 hours to 7 days after dosing.
Following a single oral doses of 1.5 or 3 g/kg bw of methanol was
reported to impair the antioxidant defenses in the liver, erythrocyte,
and serum (Skrzydlewska and Farbiszewski, 1996, 1998). A decrease
in antioxidant activity in the brain and liver following very high
