title: Effect of rimonabant, the cannabinoid CB1 receptor antagonist, on peripheral nerve in streptozotocin-induced diabetic rat.
abstract: The aim of this study is to investigate the effect of rimonabant, which has antiatherosclerotic and antiinflammatory properties, on peripheral neuropathy in a diabetic rat. Diabetic rat models were induced by treatment with streptozotocin and then either normal or diabetic rats were treated with an oral dose of 10mg/kg/day rimonabant or placebo for 24 weeks. We quantified the densities of intraepidermal (PGP9.5+) nerve fiber and total skin (RECA-1+) capillary length. We also measured the current perception threshold, as defined by the intensity of sine-wave stimulus, skin blood flow after treadmill running and TNF-alpha level in spinal cord tissue or plasma. After 24 weeks, rimonabant reduced the body weight and food intake in both diabetic and normal rats, but it had no effect on blood sugar levels. In addition, rimonabant treatment significantly improved the decreased intraepidermal nerve fiber density (5.53+/-0.12 vs. 4.36+/-0.27/mm, P<0.05) and alleviated the increased current perception threshold in rimonabant-treated versus control diabetic rats. These responses were closely associated with the attenuation of skin capillary loss (1.98+/-0.07 vs. 1.67+/-0.10 mm/mm(2), P<0.05), increase in skin blood flow (14.93+/-1.08 vs. 12.07+/-0.87 TPU, P<0.05) and reduction in TNF-alpha level in tissue (70.10+/-4.99 vs. 91.18+/-3.34 pg/mg, P<0.05) in rimonabant-treated diabetic rats compared with placebo. These findings suggest that rimonabant can be beneficial for treatment of diabetic peripheral neuropathy, possibly due to its potential role in micro- and macrovessel protection and its anti-inflammatory properties.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Wei Jing
authors.initials: WJ
authors.lastname: Liu
authors.forename: Heung Yong
authors.initials: HY
authors.lastname: Jin
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Hong Sun
authors.initials: HS
authors.lastname: Baek
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077285:Rimonabant; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013311:Streptozocin; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D001786:Blood Glucose; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D000077285:Rimonabant