scholarly journals Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ayumi Ota ◽  
Akihiro Kakehashi ◽  
Fumihiko Toyoda ◽  
Nozomi Kinoshita ◽  
Machiko Shinmura ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Aldose Reductase ◽  
Reductase Inhibitor ◽  
Motor Nerve ◽  
Positive Control ◽  
Aldose Reductase Inhibitor ◽  
Motor Nerve Conduction Velocity ◽  
Sprague Dawley ◽  
Diabetic Cataract ◽  
Long Term Treatment

We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0–6) from both lenses represented the total for each animal. DN was assessed by measuring the motor nerve conduction velocity (MNCV) in the sciatic nerve. Sorbitol and fructose levels were measured in the lens and sciatic nerve 40 weeks after diabetes onset. Cataracts developed more in untreated rats than normal rats (P<0.01). Ranirestat significantly (P<0.01) inhibited rapid cataract development; epalrestat did not. Ranirestat significantly reversed the MNCV decrease (40.7 ± 0.6 m/s) in SDT rats dose-dependently (P<0.01). Epalrestat also reversed the prevented MNCV decrease (P<0.05). Sorbitol levels in the sciatic nerve increased significantly in SDT rats (2.05 ± 0.10 nmol/g), which ranirestat significantly suppressed dose-dependently, (P<0.05, <0.01, and <0.01); epalrestat did not. Ranirestat prevents DN and cataract; epalrestat prevents DN only.

Effect of aldose reductase inhibitor on experimental diabetic cataract monitored by laser raman spectroscopy

1987 ◽  
Vol 45 (1) ◽  
pp. 185-186 ◽  
Author(s):  
Aritake Mizuno ◽  
Hiroko Nozawa ◽  
Tokikage Yaginuma ◽  
Hiroshi Matsuzaki ◽  
Yukihiro Ozaki ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Aldose Reductase ◽  
Reductase Inhibitor ◽  
Aldose Reductase Inhibitor ◽  
Laser Raman Spectroscopy ◽  
Diabetic Cataract ◽  
Laser Raman

scholarly journals Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Fumihiko Toyoda ◽  
Yoshiaki Tanaka ◽  
Ayumi Ota ◽  
Machiko Shimmura ◽  
Nozomi Kinoshita ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Aldose Reductase ◽  
Reductase Inhibitor ◽  
Retinal Thickness ◽  
Neuroprotective Effect ◽  
Treated Group ◽  
Aldose Reductase Inhibitor ◽  
Untreated Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats.Methods. The animals were divided into six groups, normal Sprague-Dawley rats(n=8), untreated SDT rats(n=9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day,n=7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day,n=7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured.Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP.Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

scholarly journals Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yiji Tu ◽  
Zenggan Chen ◽  
Feng Zhang ◽  
Zhenglin Di ◽  
Junhui Zhang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Early Phase ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Motor Nerve ◽  
Motor Nerve Conduction Velocity ◽  
Sprague Dawley ◽  
Cell Cycle Protein

Aims. To investigate the candidate biomarkers and molecular mechanisms involved in the early phase of experimental diabetic peripheral neuropathy (DPN). Methods. Diabetes in Sprague-Dawley rats was induced with streptozotocin (STZ) treatment, followed with neurological tests and histological examinations to assess the neuropathic symptoms of DPN. Microarray was performed on the sciatic nerve tissues from control rats and DPN rats at then6th week after diabetes induction, and differentially expressed genes (DEGs) between them were identified and applied for further bioinformatic analyses. Results. Experimental DPN rats were successfully constructed, presenting significantly decreased withdrawal threshold and motor nerve conduction velocity, and typical histological changes in the sciatic nerve. 597 DEGs (186 up- and 411 downregulated) were identified in DPN rats. DEGs from the 3 most highly connected clusters in the protein-protein interaction network were enriched for biological processes or pathways such as “cell division,” “cell cycle,” “protein phosphorylation,” “chemokine signaling pathway,” “neuropeptide signaling pathway,” “response to drug,” “cellular response to insulin stimulus,” “PPAR signaling pathway,” and “glycerophospholipid metabolism.” Thirteen genes were identified as the hub DEGs in the PPI network. Eleven transcriptional factors (TFs) targeting 9 of the 13 hub DEGs were predicted. Conclusions. The present study identified a pool of candidate biomarkers such as Cdk1, C3, Mapk12, Agt, Adipoq, Cxcl2, and Mmp9 and molecular mechanisms which may be involved in the early phase of experimental DPN. The findings provide clues for exploring new strategies for the early diagnosis and treatment of DPN.

Sign in / Sign up

Export Citation Format

Share Document