Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT 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.

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Dose-Dependent Reduction of Retinal Vessel Changes Associated with Diabetic Retinopathy in Galactose-Fed Dogs by the Aldose Reductase Inhibitor M79175

Journal of Ocular Pharmacology and Therapeutics ◽

10.1089/jop.1997.13.517 ◽

1997 ◽

Vol 13 (6) ◽

pp. 517-528 ◽

Cited By ~ 29

Author(s):

HEIKE NEUENSCHWANDER ◽

YUKIO TAKAHASHI ◽

PETER F. KADOR

Keyword(s):

Diabetic Retinopathy ◽

Aldose Reductase ◽

Reductase Inhibitor ◽

Retinal Vessel ◽

Aldose Reductase Inhibitor ◽

Dose Dependent

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Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.5.e965 ◽

1997 ◽

Vol 273 (5) ◽

pp. E965-E971 ◽

Cited By ~ 5

Author(s):

Nigishi Hotta ◽

Jiro Nakamura ◽

Fumihiko Sakakibara ◽

Yoji Hamada ◽

Tomohiro Hara ◽

...

Keyword(s):

Animal Model ◽

Diabetic Retinopathy ◽

Aldose Reductase ◽

Reductase Inhibitor ◽

Polyol Pathway ◽

Aldose Reductase Inhibitor ◽

Dependent Diabetes Mellitus ◽

Pathway Activity ◽

Oletf Rats ◽

Long Evans

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.

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Chemopreventive Properties and Toxicity of Kelulut Honey inSprague DawleyRats Induced with Azoxymethane

BioMed Research International ◽

10.1155/2016/4036926 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Latifah Saiful Yazan ◽

Muhamad Firdaus Shyfiq Muhamad Zali ◽

Razana Mohd Ali ◽

Nurul Amira Zainal ◽

Nurulaidah Esa ◽

...

Keyword(s):

Antioxidant Activities ◽

Treated Group ◽

Aberrant Crypt Foci ◽

Untreated Group ◽

Sprague Dawley ◽

Blood Profile ◽

Chemopreventive Agents ◽

Treatment Groups ◽

Aberrant Crypts ◽

Sprague Dawley Rats

Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees fromTrigonaspecies and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources.Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM).Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM. Injection of AOM (15 mg/kg) was via intraperitoneal route once a week for two subsequent weeks. The treatment groups were given oral administration of KH (1183 mg/kg body weight) twice daily for 8 weeks.Results. Treatment with KH significantly reduced the total number of aberrant crypt foci (ACF) and aberrant crypts (AC) and crypt multiplicity. KH was not toxic to the animals since the level of blood profile parameters, liver enzymes, and kidney functions was in normal range.Conclusions. The current finding shows that KH has chemopreventive properties in rats induced with colorectal cancer and also was found not toxic towards the animals.

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Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/2015.9.spine15628 ◽

2016 ◽

Vol 25 (1) ◽

pp. 114-124 ◽

Cited By ~ 13

Author(s):

Sergiy V. Kushchayev ◽

Morgan B. Giers ◽

Doris Hom Eng ◽

Nikolay L. Martirosyan ◽

Jennifer M. Eschbacher ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuroprotective Effect ◽

Scar Tissue ◽

Treated Group ◽

Secondary Injury ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Cord Injury ◽

Behavioral Assessments

OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

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The effect of the aldose reductase inhibitor, ponalrestat, on the progression of diabetic retinopathy

Journal of Diabetes and its Complications ◽

10.1016/1056-8727(92)90024-f ◽

1992 ◽

Vol 6 (2) ◽

pp. 131-137 ◽

Cited By ~ 23

Author(s):

Carlos Arauz-Pacheco ◽

Luis C. Ramirez ◽

Lourdes Pruneda ◽

George E. Sanborn ◽

Julio Rosenstock ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Aldose Reductase ◽

Reductase Inhibitor ◽

Aldose Reductase Inhibitor

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

Journal of Diabetes Research ◽

10.1155/2013/175901 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 6

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.

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