Thirteen-month inhibition of aldose reductase by zenarestat prevents morphological abnormalities in the dorsal root ganglia of streptozotocin-induced diabetic rats.
The dorsal root ganglia (DRG) have been identified as the target tissue in diabetic somatosensory neuropathy. It has been reported that, in the chronically diabetic state, DRG sensory neurons may undergo morphological changes. In this study, we examined the effect of zenarestat, an aldose reductase inhibitor, on the morphological derangement of the DRG and the sural nerve of streptozotocin-induced diabetic rats (STZ rats) over a 13-month period. The cell area of the DRG in STZ rats was smaller than that in normal rats. A decrease in fiber size was apparent in the sural nerve of the STZ rats, and the fiber density was greater. These morphological changes were reversed in zenarestat-treated STZ rats. The data suggest that, in peripheral sensory diabetic neuropathy, hyperactivation of the polyol pathway induces abnormalities not only in peripheral nerve fiber, but also in the DRG, which is an aggregate of primary sensory afferent cell bodies.
Shimoshige
Yukinori
Y
Pharmacology Research Labs, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. yukinori.shimoshige@jp.astellas.com
Minoura
Kyoko
K
Matsuoka
Nobuya
N
Takakura
Shoji
S
Mutoh
Seitaro
S
Kamijo
Mikiko
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D011108:Polymers / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013497:Sural Nerve / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology
D004791:Enzyme Inhibitors; D011108:Polymers; D011799:Quinazolines; C024617:polyol; C064920:FR 74366; D000449:Aldehyde Reductase