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Aldose Reductase Inhibitor
Aldose reductase inhibitors are a class of drugs to prevent
damage to the nerves and eyes in people with diabetes mellitus.
Diabetes mellitus is a complex, long-term disorder in which the
body is not able to effectively use a natural chemical called insulin.
Insulin's main job is to quickly absorb glucose (a type of sugar) from the blood into cells
for their energy needs and into the fat and liver (a large organ that performs many
chemical tasks) cells for storage. Examples of medications classified as aldose
reductase inhibitors are epalrestat (see above; brand names: Eparel 50, Aldonil, Alrista),
fidarestat (SNK-860), ranirestat (AS-3201), and tolrestat (brand name: Alredase). The
latter was discontinued in 1997 due to the risk of severe liver damage and death.
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Aldose reductase inhibitors are so named because they inhibit (work against) the actions
of an enzyme known as aldose reductase. An enzyme is a type of protein that helps
produce chemical reactions in the body. Aldose reductase is a type of enzyme that is
normally present in many parts of the body.
Aldose reductase helps take glucose and forms a sugar alcohol known as sorbitol.
Glucose is classified as a type of simple sugar known as aldoses. Reductase refers to
the chemical process (reduction) by which these chemical transformation occur. This
helps explain the name “aldose reductase.”
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In people with diabetes, when glucose levels increase in tissues of
the body that are not sensitive to the effects of insulin, aldose
reductase activity increases to absorb the glucose. The problem is
that since it creates sorbitol, sorbitol levels increase because they
cannot pass through the cell membrane easily. This results in
osmotic stress/damage which is when water is drawn into the cell(s)
causing harm. This process results in damage to the nerves and
eyes in people with diabetes. Areas in the body that are not
sensitive to the effects of insulin include the lens of the eye, nerves
that supply body areas outside the brain or spinal cord, and the
glomerulus. The glomerulus is a network of capillaries (tiny blood
vessels) in the kidneys that performs the first step of filtering blood.
