All-trans retinoic acid induces nerve regeneration and increases serum and nerve contents of neural growth factor in experimental diabetic neuropathy

• Published in: Translational research : the journal of laboratory and clinical medicine 2008-07, Vol.152 (1), p.31-37
• Main Authors: Hernández-Pedro, Norma, Ordóñez, Graciela, Ortiz-Plata, Alma, Palencia-Hernández, Guadalupe, García-Ulloa, Ana Cristina, Flores-Estrada, Diana, Sotelo, Julio, Arrieta, Oscar
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - analysis; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - pathology; Diabetic Neuropathies - prevention & control; Drug Evaluation, Preclinical; Internal Medicine; Male; Mice; Nerve Growth Factor - blood; Nerve Growth Factor - metabolism; Nerve Regeneration - drug effects; Random Allocation; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Sciatic Nerve - ultrastructure; Tretinoin - pharmacology; Tretinoin - therapeutic use
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2008.05.007

Local diminution of the neural growth factor (NGF) contributes to the apparition of diabetic neuropathy. All-trans retinoic acid (RA) increases the expression of neural growth factor and its receptor participating in translation pathways. This study evaluates RA as a treatment of diabetic neuropathy: 120 mice were assigned randomly to 4 groups. Group A (n = 30) was taken as control; group B (n = 30) received 50 mg/kg intraperitoneal streptozotocin (STZ); group C (n = 30) received STZ, and after diabetic neuropathy developed, they were treated with subcutaneous RA 20 mg/kg daily during 60 days; and group D (n = 30) only received RA. Plasma glucose, thermosensitive tests, serum, and the nerve contents of NGF were measured in all animals. Evaluation by electron microscopy was performed in search of morphologic changes secondary to neuropathy and nerve regeneration. Diabetic mice had an increased threshold to pain. Treatment with RA in diabetic mice reverted changes in sensitivity as compared with diabetic mice that received placebo ( P < 0.001). No differences in pain threshold among controls, RA, and diabetes mellitus (DM) + RA groups were found. Glucose levels were not affected by the treatment with RA. NGF diminished significantly in the sciatic nerve in diabetic mice as compared with controls and with the RA group. Animals with DM + RA had a significant increase of NGF in nerves as compared with the other groups. RA also regressed the ultrastructural changes induced by diabetes that showed increased neural regeneration. RA can revert functional and ultrastructural changes and induce neural regeneration after the establishment of diabetic neuropathy, possibly because of the increased of NGF concentrations in nerve terminals.