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Retinoic acid increases tissue and plasma contents of nerve growth factor and prevents neuropathy in diabetic mice.

Arrieta O, García-Navarrete R, Zúñiga S, Ordóñez G, Ortiz A, Palencia G, Morales-Espinosa D, Hernández-Pedro N, Sotelo J

Neuroimmunology Unit, National Institute of Neurology and Neurosurgery of Mexico, Insurgentes Sur 3877, 14269 Mexico City, Mexico. ogar@servidor.unam.mx

BACKGROUND: Decreased production of nerve growth factor (NGF) may contribute to diabetic neuropathy; however, exogenous administration of NGF induces only a modest benefit. Retinoic acid (RA) promotes the endogenous expression of nerve growth factor and its receptor. We studied the effects of RA on diabetic neuropathy in mice with streptozotocin-induced diabetes. MATERIAL AND METHODS: One hundred and twenty National Institutes of Health (NIH) albino mice randomly separated into three groups (A, n = 30; B, n = 30; C, n = 60). Diabetes mellitus was induced with streptozotocin in groups A and B. Animals from group A received a subcutaneous injection of 25 microl of mineral oil daily for 90 days, while those from group B received a subcutaneous injection of 20 mg kg(-1) of all trans RA. Animals from group C were taken as controls. At the end of the experiment, blood glucose and NGF levels (both in serum and sciatic nerve) were measured. Two behavioural tests were conducted in a blind fashion to detect abnormalities of thermal and nociceptive thresholds. RESULTS: Contents of NGF in healthy untreated mice were 1490 +/- 190 pg mg(-1) in nerve and 113 +/- 67 pg mg(-1) in serum; in diabetic untreated mice the values were 697 +/- 219 pg mL(-1) in nerve and 55 +/- 41 pg mL(-1) in serum; and in diabetic mice treated with RA the values were 2432 +/- 80 pg mL(-1) in nerve and 235 +/- 133 pg mg(-1) in serum (P < 0.002). Ultrastructural evidence of nerve regeneration and sensitivity tests improved in diabetic mice treated with RA as compared with nontreated diabetic mice. CONCLUSION: Our findings indicate that administration of RA increases serum and nerve contents of NGF in diabetic mice and suggest a potential therapeutic role for retinoic acid in diabetic patients.

Published 28 February 2005 in Eur J Clin Invest, 35(3): 201-7.
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