| Research Abstract |
In poorly controlled diabetic patients and streptozotocin-induced diabetic rats, neutrophil bactericidal function (oxygen-derived free radicals generation) was clearly decreased. Especially, the generation of superoxide anion and the myeloperoxidase (MPO) dependent radicals were reduced compaired to control. The MPO activity was also decreased in neutrophils from poorly controlled diabetic patients, which was correlated to the increase in HbA1c.
Two drugs, granulocyte-colony stimulating facto (G-CSF) and epairestat, an aldose reductase inhibitor, were improved the diabetic-induced decrease in the generation of oxygen-derived free radicals by poorly controlled diabetic patients and diabetic rats. This improvement by G-CSF was more significant in patients with more poorly blood glucose control. In diabetic rats, cytosolic sorbitol concentration was increased. Epalrestat not only suppressed this increase in sorbitol concentration but increased the impaired neutrophil bactericidal function. There was a negative correlation between epairestat-induced decrease in sorbitol concentration and epairestat-induced increase in neutrophil bactericidal function.
It is well known that the susceptibility to infection is dependent on the impaired neutrophils bactericidal function. This study suggested that the susceptibility to infection in diabetes may be due to the impairment of the generation of oxygen-derived free radicals by neutrophils. Some drugs (e.g. (G-CSF and epairestat) may be useful as drug to prevent the susceptibility to infection in diabetes.
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