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Updates on Oxaliplatin-Induced Peripheral Neurotoxicity (OXAIPN)
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Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Experimental Neurology Unit, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza (MB), Italy
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Academic Editor: David Bellinger
Toxics 2015, 3(2), 198-223; https://doi.org/10.3390/toxics3020198
Received: 24 April 2015 / Revised: 26 May 2015 / Accepted: 1 June 2015 / Published: 5 June 2015
(This article belongs to the Special Issue Toxicities of Therapeutic Agents Used in Medicine)
The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related dysregulation of pathways involving calcium signalling, reactive oxygen species and apoptosis. Vincristine is able to affect calcium movement through the Dorsal Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and leading to abnormal neuronal excitability. Paclitaxel induces the opening of the mitochondrial permeability transition pore in axons followed by mitochondrial membrane potential loss, increased reactive oxygen species generation, ATP level reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover, the expression of a certain number of genes, including those controlling mitochondrial functions, was altered in patients with bortezomib-induced peripheral neuropathy. View Full-Text
Keywords: Chemotherapy compounds; peripheral neurotoxicity; neuropathic pain; mitochondria; mitotoxicity Chemotherapy compounds; peripheral neurotoxicity; neuropathic pain; mitochondria; mitotoxicity
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Canta, A.; Pozzi, E.; Carozzi, V.A. Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN). Toxics 2015, 3, 198-223.

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