title: Retinoic acid reduces solvent-induced neuropathy and promotes neural regeneration in mice.
abstract: In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid.
authors.affiliation: Neuroimmunology Unit, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Palencia
authors.forename: Norma
authors.initials: N
authors.lastname: Hernández-Pedro
authors.forename: David
authors.initials: D
authors.lastname: Saavedra-Perez
authors.forename: Omar
authors.initials: O
authors.lastname: Peña-Curiel
authors.forename: Alma
authors.initials: A
authors.lastname: Ortiz-Plata
authors.forename: Graciela
authors.initials: G
authors.lastname: Ordoñez
authors.forename: Diana
authors.initials: D
authors.lastname: Flores-Estrada
authors.forename: Julio
authors.initials: J
authors.lastname: Sotelo
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
mesh_terms: D000818:Animals; D051379:Mice; D020932:Nerve Growth Factor / Q000097:blood; D009416:Nerve Regeneration / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D012997:Solvents; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D012997:Solvents; D014212:Tretinoin; D020932:Nerve Growth Factor
keywords: all-trans retinoic acid treatment; nerve growth factor; neural regeneration; organic solvent exposure; peripheral neuropathy