AUTORADIOGRAPHIC IMAGING OF FORMALDEHYDE ADDUCTS IN MICE - POSSIBLE RELEVANCE FOR VASCULAR DAMAGE IN DIABETES

The activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be elevated in blood from diabetic patients. It has been s uggested that the enzyme is involved in the development of complicatio ns such as retinopathies, nephropathies and neuropathies, which are as sociated with advanced diabetes, possibly by the formation of toxic me tabolites. Under the influence of SSAO, methylamine is deaminated to f ormaldehyde which is known to react with various macromolecules. It ha s therefore been proposed that specific inhibition of SSAO could be of therapeutic value for treatment of diabetic patients. The present res ults provide evidence that treatment with an SSAO inhibitor potently r educes the levels of irreversible adducts. In this study, C-14-methyla mine was given intraperitoneally to NMRI mice, and the tissue distribu tion of irreversibly bound methylamine metabolites was estimated by an autoradiographic method. Such radioactive residues occurred in high c oncentrations in the intestinal wall, brown adipose tissue, spleen and bone marrow. By inhibiting SSAO irreversibly with hydralazine before giving C-14-methylamine to the mice, it was possible to determine the resynthesis rate of SSAO in different tissues. A complete recovery of SSAO activity was seen in the intestinal wall after 6 days, whereas on ly about 60% was recovered in adipose tissue after 14 days. This sugge sts that factors controlling the synthesis of SSAO differ in these tis sues, or that these tissues express different forms of enzymes.