title: Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model.
abstract: Pre-existing neuropathy, a not uncommon feature in oncologic patients, is a potential but non-confirmed risk factor to develop early or severe chemotherapy-induced neuropathy. The main goal of this study is to evaluate the role of pre-existing neuropathy induced by vincristine (VNC) or bortezomib (BTZ) as a risk factor to develop more severe BTZ-induced neuropathy in a mouse model. VNC, at doses of 1 and 1.5 mg/kg given twice per week for 4 weeks, induced a moderate and severe sensory-motor neuropathy, primarily axonal, with predominant involvement of myelinated sensory axons. The neuropathy induced by BTZ at dose of 1 mg/kg given twice per week for 6 weeks was a mild axonal sensory neuropathy involving myelinated and unmyelinated fibers. The neuropathy in mice previously treated and retreated with the same schedule of BTZ after 4 weeks of washout period was similar in profile and severity to the one observed after the first treatment. When basal neuropathy was classified as moderate (most of BTZ-treated animals) or severe (all VNC-treated animals and two BTZ-treated animals), there was a more marked decline in sensory nerve function during BTZ retreatment in the group with basal severe neuropathy (-86%) than in the groups with basal mild (-57%) or without neuropathy (-52%; p < 0.001). Histopathological findings supported the functional results. Therefore, this study shows that the presence of a severe neuropathy previous to treatment with an antitumoral agent, such as BTZ, results in a more marked involvement of peripheral nerves.
authors: Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors: Jordi
authors: J
authors: Bruna
authors: Albert
authors: A
authors: Alé
authors: Roser
authors: R
authors: Velasco
authors: Jessica
authors: J
authors: Jaramillo
authors: Xavier
authors: X
authors: Navarro
authors: Esther
authors: E
authors: Udina
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001897:Boronic Acids / Q000633:toxicity*; D000069286:Bortezomib; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000473:pathology* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D011719:Pyrazines / Q000633:toxicity*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib