The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats

Shimoshige, Yukinori; Ikuma, Kyoko; Yamamoto, Tadashi; Takakura, Shoji; Kawamura, Ikuo; Seki, Jiro; Mutoh, Seitaro; Goto, Toshio

doi:10.1053/meta.2000.17723

Cited by 37 publications

(20 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The decreases in motor conduction velocity and CMAPs detected in the female ZDF rat are also similar to those reported in male ZDF rats (Shibata et al, 2000;Shimoshige et al, 2000;Oltman et al, 2005;Li et al, 2006). Previous examinations of DN in the ZDF rat were performed only in frankly diabetic male animals, (Shibata et al, 2000;Shimoshige et al, 2000;Oltman et al, 2005;Li et al, 2006). We detect similar deficits in the female ZDF-N animals.…”

Section: Discussionsupporting

confidence: 87%

“…Diabetic neuropathy (DN) is reported in ZDF rats and demonstrated by decreased motor nerve conduction velocity (MNCV), decreased sensory nerve conduction velocity (SNCV) and decreased levels of calcitonin gene-related peptide (Shibata et al, 2000;Shimoshige et al, 2000;Oltman et al, 2005;Li et al, 2006). All of these studies were performed in male diabetic ZDF rats; therefore this study is the first comparison of diabetes and IGT in the female ZDF rat.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative injury and neuropathy in diabetes and impaired glucose tolerance

Russell

Berent-Spillson

Vincent

et al. 2008

Neurobiology of Disease

View full text Add to dashboard Cite

Clinical studies suggest that impaired glucose tolerance (IGT) is associated with the development of neuropathy. The aim of the current study was to determine if neuropathy developed in the female Zucker Diabetic Fatty (ZDF) rat, an animal model of IGT and type 2 diabetes. The ZDF rat develops impaired glucose tolerance (IGT) when fed a control diet, and frank diabetes when fed a high fat diet. Following 10 weeks of hyperglycemia, sensory nerve action potentials (SNAP) and compound motor action potentials (CMAP) were reduced and sensory conduction velocities were slowed (distal > proximal) in the tail and hind limb in ZDF animals with IGT and frank diabetes (p<0.01). Neuropathy was coupled with evidence of increased reactive oxygen species (ROS) and cellular injury in dorsal root ganglion (DRG) neurons from IGT animals. Our study supports the hypothesis that neuropathy develops in an animal model of IGT and is associated with evidence of oxidative injury in DRG and peripheral nerves.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Oxidative injury and neuropathy in diabetes and impaired glucose tolerance

Russell

Berent-Spillson

Vincent

et al. 2008

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…Decreased motor and sensory nerve conduction velocity have been described in ZDF rats (Shimoshige et al., 2000; Oltman et al., 2005; Li et al., 2006) and electrophysiological properties of C‐fibres have been previously reported in the streptozotocin model (Chen and Levine, 2001; Suzuki et al., 2002b; Fuchs et al., 2010); however, no data were found on the mechanical sensitivity of primary afferent nociceptive fibres in a model of type 2 diabetes. In our study the Aδ‐fibres were selected because main behavioural changes are related to tactile allodynia and hyperalgesia and they respond to mechanical stimulation (Basbaum et al., 2009) even better than C‐fibres.…”

Section: Discussionmentioning

confidence: 99%

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Paniagua

Girón

Goicoechea

et al. 2016

European Journal of Pain

View full text Add to dashboard Cite

BackgroundE‐52862 (S1RA, 4‐[2‐[[5‐methyl‐1‐(2‐naphthalenyl)‐1H‐pyrazol‐3‐yl]oxy]ethyl]‐morpholine), a novel selective sigma 1 receptor (σ1R) antagonist, has demonstrated efficacy in nociceptive and neuropathic pain models. Our aim was to test if σ1R blockade with E‐52862 may modify the signs of neuropathy in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model.MethodsMechanical and thermal response thresholds were tested on 7‐, 13‐, 14‐ and 15‐week‐old ZDF rats treated with saline or with E‐52862 acutely administered on week 13, followed by sub‐chronic administration (14 days). Axonal peripheral activity (skin–saphenous nerve preparation) and isolated aorta or mesenteric bed reactivity were analysed in 15‐week‐old ZDF rats treated with saline or E‐52862 and in LEAN rats.ResultsZucker diabetic fatty rats showed significantly decreased thermal withdrawal latency and threshold to mechanical stimulation on week 13 compared to week 7 (prediabetes) and with LEAN animals; single‐dose and sub‐chronic E‐52862 administration restored both parameters to those recorded on week 7. Regarding axonal peripheral activity, E‐52862 treatment increased the mean mechanical threshold (77.3 ± 21 mN vs. 19.6 ± 1.5 mN, saline group) and reduced the response evoked by mechanical increasing stimulation (86.4 ± 36.5 vs. 352.8 ± 41.4 spikes) or by repeated mechanical supra‐threshold steps (39.4 ± 1.4 vs. 83.5 ± 0.9). E‐52862 treatment also restored contractile response to phenylephrine in aorta and mesenteric bed.ConclusionsE‐52862 administration reverses neuropathic (behavioural and electrophysiological) and vascular signs in the ZDF rat.SignificanceBlockade of σ1R avoids the development of diabetic neuropathy in rats, and may represent a potentially useful therapeutic approach to peripheral neuropathies in diabetic patients.What does this study add? This study presents evidences for the potential usefulness of sigma receptor blockade on diabetic neuropathy in rats.The methodology includes behavioural evidences, electrophysiological data and vascular‐isolated models.

show abstract

“…Zenarestat, orally administrated at a dose of 3.2 mg/kg/day for 8 weeks, had no significant effect on the delay in F-wave minimal latency and the slowing of motor nerve conduction velocity, although the sorbitol accumulation in the sciatic nerve was partially inhibited. On the other hand, 32 mg/kg zenarestat treatment improved these nerve dysfunctions, along with a reduction of nerve sorbitol accumulation almost to the normal level [100]. Obviously, zenarestat could improve diabetic peripheral neuropathy in Zucker diabetic fatty rats.…”

Section: Zenarestatmentioning

confidence: 89%

Aldose Reductase Inhibitors as Potential Therapeutic Drugs of Diabetic Complications

Zhu¹

2013

Diabetes Mellitus - Insights and Perspectives

View full text Add to dashboard Cite

The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats

Cited by 37 publications

References 26 publications

Oxidative injury and neuropathy in diabetes and impaired glucose tolerance

Oxidative injury and neuropathy in diabetes and impaired glucose tolerance

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Aldose Reductase Inhibitors as Potential Therapeutic Drugs of Diabetic Complications

Contact Info

Product

Resources

About