Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy
Distal sensory-motor polyneuropathy is one of the most frequent diabetic complications. However, few therapies address the etiology of neurodegeneration in the peripheral nervous systems of diabetic patients. Several metabolic mechanisms have been proposed as etiologies of this polyneuropathy. In th...
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| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/2756020 |
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| author | Saeko Asano Tatsuhito Himeno Tomohide Hayami Mikio Motegi Rieko Inoue Hiromi Nakai-Shimoda Emiri Miura-Yura Yoshiaki Morishita Masaki Kondo Shin Tsunekawa Yoshiro Kato Koichi Kato Keiko Naruse Jiro Nakamura Hideki Kamiya |
| author_facet | Saeko Asano Tatsuhito Himeno Tomohide Hayami Mikio Motegi Rieko Inoue Hiromi Nakai-Shimoda Emiri Miura-Yura Yoshiaki Morishita Masaki Kondo Shin Tsunekawa Yoshiro Kato Koichi Kato Keiko Naruse Jiro Nakamura Hideki Kamiya |
| author_sort | Saeko Asano |
| collection | DOAJ |
| description | Distal sensory-motor polyneuropathy is one of the most frequent diabetic complications. However, few therapies address the etiology of neurodegeneration in the peripheral nervous systems of diabetic patients. Several metabolic mechanisms have been proposed as etiologies of this polyneuropathy. In this study, we revisited one of those mechanisms, the polyol pathway, and investigated the curative effects of a novel strong aldose reductase inhibitor, ranirestat, in streptozotocin-induced diabetic rats with preexisting polyneuropathy. Twelve weeks after the onset of diabetes, rats which had an established polyneuropathy were treated once daily with a placebo, ranirestat, or epalrestat, over 6 weeks. Before and after the treatment, nerve conduction velocities and thermal perception threshold of hindlimbs were examined. After the treatment, intraepidermal fiber density was evaluated. As an ex vivo assay, murine dorsal root ganglion cells were dispersed and cultured with or without 1 μmol/l ranirestat for 48 hours. After the culture, neurite outgrowth was quantified using immunological staining. Sensory nerve conduction velocity increased in diabetic rats treated with ranirestat (43.3±3.6 m/s) compared with rats treated with placebo (39.8±2.3). Motor nerve conduction velocity also increased in the ranirestat group (45.6±3.9) compared with the placebo group (38.9±3.5). The foot withdrawal latency to noxious heating was improved in the ranirestat group (17.7±0.6 seconds) compared with the placebo group (20.6±0.6). The decrease in the intraepidermal fiber density was significant in the diabetic placebo group (21.6±1.7/mm) but not significant in the diabetic ranirestat group (26.2±1.2) compared with the nondiabetic placebo group (30.3±1.5). Neurite outgrowth was promoted in the neurons supplemented with ranirestat (control 1446±147 μm/neuron, ranirestat 2175±149). Ranirestat improved the peripheral nervous dysfunctions in rats with advanced diabetic polyneuropathy. Ranirestat could have potential for regeneration in the peripheral nervous system of diabetic rats. |
| format | Article |
| id | doaj-art-92565764ef2c4923829e40a620f80c3c |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-92565764ef2c4923829e40a620f80c3c2025-02-03T05:51:19ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/27560202756020Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic PolyneuropathySaeko Asano0Tatsuhito Himeno1Tomohide Hayami2Mikio Motegi3Rieko Inoue4Hiromi Nakai-Shimoda5Emiri Miura-Yura6Yoshiaki Morishita7Masaki Kondo8Shin Tsunekawa9Yoshiro Kato10Koichi Kato11Keiko Naruse12Jiro Nakamura13Hideki Kamiya14Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDepartment of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, JapanDepartment of Internal Medicine, Aichi Gakuin University School of Dentistry, Nagoya, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDivision of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, JapanDistal sensory-motor polyneuropathy is one of the most frequent diabetic complications. However, few therapies address the etiology of neurodegeneration in the peripheral nervous systems of diabetic patients. Several metabolic mechanisms have been proposed as etiologies of this polyneuropathy. In this study, we revisited one of those mechanisms, the polyol pathway, and investigated the curative effects of a novel strong aldose reductase inhibitor, ranirestat, in streptozotocin-induced diabetic rats with preexisting polyneuropathy. Twelve weeks after the onset of diabetes, rats which had an established polyneuropathy were treated once daily with a placebo, ranirestat, or epalrestat, over 6 weeks. Before and after the treatment, nerve conduction velocities and thermal perception threshold of hindlimbs were examined. After the treatment, intraepidermal fiber density was evaluated. As an ex vivo assay, murine dorsal root ganglion cells were dispersed and cultured with or without 1 μmol/l ranirestat for 48 hours. After the culture, neurite outgrowth was quantified using immunological staining. Sensory nerve conduction velocity increased in diabetic rats treated with ranirestat (43.3±3.6 m/s) compared with rats treated with placebo (39.8±2.3). Motor nerve conduction velocity also increased in the ranirestat group (45.6±3.9) compared with the placebo group (38.9±3.5). The foot withdrawal latency to noxious heating was improved in the ranirestat group (17.7±0.6 seconds) compared with the placebo group (20.6±0.6). The decrease in the intraepidermal fiber density was significant in the diabetic placebo group (21.6±1.7/mm) but not significant in the diabetic ranirestat group (26.2±1.2) compared with the nondiabetic placebo group (30.3±1.5). Neurite outgrowth was promoted in the neurons supplemented with ranirestat (control 1446±147 μm/neuron, ranirestat 2175±149). Ranirestat improved the peripheral nervous dysfunctions in rats with advanced diabetic polyneuropathy. Ranirestat could have potential for regeneration in the peripheral nervous system of diabetic rats.http://dx.doi.org/10.1155/2019/2756020 |
| spellingShingle | Saeko Asano Tatsuhito Himeno Tomohide Hayami Mikio Motegi Rieko Inoue Hiromi Nakai-Shimoda Emiri Miura-Yura Yoshiaki Morishita Masaki Kondo Shin Tsunekawa Yoshiro Kato Koichi Kato Keiko Naruse Jiro Nakamura Hideki Kamiya Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy Journal of Diabetes Research |
| title | Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy |
| title_full | Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy |
| title_fullStr | Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy |
| title_full_unstemmed | Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy |
| title_short | Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy |
| title_sort | ranirestat improved nerve conduction velocities sensory perception and intraepidermal nerve fiber density in rats with overt diabetic polyneuropathy |
| url | http://dx.doi.org/10.1155/2019/2756020 |
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