Correction of diabetic neuropathies using aldose reductase inhibitors and Picamilone

Kuchmerovskaia TM, Parkhomets PK, Donchenko GV, Obrosova IG,
Klimenko AP, Kuchmerovskii NA, Pakirbaeva LV, Efimov AS.

[Article in Russian]

Institute of Biochemistry, Kiev.

Abstract

Streptosotocin-induced diabetes in rats is accompanied by the development of diabetic complications such as neuropathies. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation.  Aldose reductase inhibitors (AL-1576, sorbinil) administration leads to partial restoration of serotonin and GABA release, while picamilone restored only GABA release.  It was shown that Na+,K(+)-ATPase activities decreased in synaptosomes, synaptic membranes and sciatic nerve of diabetic rats compared to control.  Administration of AL-1576 normalized Na+, K(+)-ATPase activity, while sorbinil and picamilone less effectively.  Sorbitol level are increased in streptozotocin-diabetic rats as compared to control.  The picamilone and aldose reductase inhibitors administration to diabetic rats is accompanied by the partial reduction of brain sorbitol level.  The findings confirm the important role of picamilone and aldose reductase inhibitors in the prevention and treatment of diabetic neuropathy.

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