Special Issue "Toxicities of Therapeutic Agents Used in Medicine"

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A special issue of Toxics (ISSN 2305-6304).

Deadline for manuscript submissions: 30 April 2015

Special Issue Editors

Guest Editor
Prof. Guido Cavaletti
Unità di Neurologia Sperimentale e Centro di Neuroscienze di Milano, Dipartimento di Chirurgia e Medicina traslazionale, Università di Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy
Website: http://www.enu.dcmt.unimib.it/doctor/guido-cavaletti/
E-Mail: guido.cavaletti@unimib.it
Interests: peripheral neuropathies; antineoplastic drugs; animal models; clinical trials

Guest Editor
Dr. Valentina Carozzi
Unità di Neurologia Sperimentale e Centro di Neuroscienze di Milano, Dipartimento di Chirurgia e Medicina traslazionale, Università di Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy
Website: http://www.enu.dcmt.unimib.it/doctor/valentina-carozzi/
E-Mail: valentina.carozzi1@unimib.it
Interests: peripheral neuropathies, antineoplastic drugs, animal models

Special Issue Information

Dear Colleagues,

Pharmacological treatment of human disorders has afforded a remarkable improvement in the management of severe illnesses, but the use of effective drugs can also be associated with “off-target” side effects which might have an impact on the survival and/or the patients’ quality of life.

Among the wide spectrum of toxicities, neurotoxicity represents one of the main concerns since the nervous system has limited capacity to recover from damage and supportive treatments are frequently ineffective.

The central nervous system is protected by the blood-brain barrier and most of the putative toxic agents are unable to cross the intact barrier, but this protection might be overcome by the administration of very high doses of drugs or might be less effective in the course of diseases such as brain tumours and infections. However, the peripheral nervous system is much less effectively protected and specific regions, such as the dorsal root ganglia, allow a very easy access to toxic substances reaching the nervous system through the bloodstream.

A full comprehension of the possible neurotoxicity of systemic as well as of local treatments represents a cornerstone in the knowledge of any physician, and it should not be limited to specialists in clinical neurosciences. The aim of this Special Issue is to provide the necessary background to enhance this comprehension, with a focus on the most frequent clinical syndromes in different fields of medicine.

Prof. Guido Cavaletti
Dr. Valentina Carozzi
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • nervous system
  • toxicity
  • clinical
  • animal models
  • diagnosis
  • treatment

Published Papers

No papers have been published in this special issue yet, see below for planned papers.

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Mitocondrial Disfunction in CIPN
Authors:
A. Canta 1, E. Pozzi 1 and V.A. Carozzi 1,2
Affiliations:
1Department of Surgery and Translational Medicine, University of Milan-Bicocca, Via Cadore 48, 20900 Monza (MB), Italy; Phone: +39-02 6448 8122  Fax: +39-02 6448 8250
2Young Against Pain Group
Abstract: The mitochondrial dysfunction has a critical role in several disorders including chemotherapy-induced painful peripheral neuropathies (CIPPN). This is due to a related disregulation 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 a loss of mitochondrial membrane potential, increased generation of reactive oxygen species, a reduction in ATP level, calcium release and mitochondrial swelling. Cisplatin, forms 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. Moreover, changes in the expression in a number of genes including those of controlling mitochondrial functions were altered in patients with paclitaxel, vincristine and bortezomib-induced peripheral neuropathy.

Type of paper: Review
Title:
L-dopa and Brain Serotonin System Dysfunction
Authors:
Branden J. Stansley and Bryan K. Yamamoto
Affiliation:
University of Toledo College of Medicine, Toledo, OH 43614, USA; E-Mail: Bryan.Yamamoto@utoledo.edu (B.K.Y.)
Abstract:
L-dopa is used to treat the motor symptoms associated with Parkinson’s disease, a neurodegenerative disorder characterized by a loss of dopamine neurons. L-dopa is the precursor to dopamine and crosses the blood-brain barrier to elevate dopamine content. The review will show that dopamine produced from L-dopa is mediated in part by serotonin neurons. Evidence will be presented showing that increases in dopamine cause oxidative stress which damages serotonin neurons. Similarly, chronic L-dopa produces deficits in serotonin neurotransmission, including decreases in both serotonin cell bodies within the dorsal raphe and serotonin neurotransmitter concentrations in several forebrain regions. Since serotonin is involved in many important physiological processes including mood and cognition, L-dopa induced serotonin deficits may play a role in the side effect symptoms observed in Parkinson’s disease patients treated with L-dopa.

Type of paper: Review
Title:
Current View in Platinum Drugs Mechanisms of Peripheral Neurotoxicity
Authors:
Alessia Chiorazzi, Sara Semperboni and Paola Marmiroli
Affiliation:
Department of Surgery and Translational Medicine, University of Milano-Bicocca, Monza (MB), Italy; E-Mail: alessia.chiorazzi@unimib.it (A.C.)
Abstract:
Peripheral neurotoxicity is the dose-limiting factor for the clinical use of platinum derivatives that are a class of anticancer drugs which includes cisplatin, carboplatin and oxaliplatin. In particular cisplatin and oxaliplatin induce a severe peripheral neurotoxicity while carboplatin is less neurotoxic.
The mechanisms proposed to explain neurotoxicity of these drugs are alteration of dorsal root ganglia, involvement of oxidative stress and mitochondrial dysfunction. Oxaliplatin also causes an acute and reversible painful neuropathy, supposed to be caused by a transient dysfunction of the voltage-gated sodium channels of peripheral nerves. Recent studies suggest that individual genetic variation may play a role in the pathogenesis of platinum drugs neurotoxicity.
Even though many mechanisms explaining neurotoxicity of these drugs have been proposed, the pathogenesis is far to be clearly defined.
In this review we will summarize the current knowledge and the most up-to-date hypothesis on the pathogenesis of this kind of peripheral neuropathy.

Type of paper: Review
Title:
Taxane-Induced Peripheral Neuropathy
Authors:
Roser Velasco 1,2 and Jordi Bruna 1,2
Affiliation:
1          Unit of Neuro-Oncology, Hospital Universitari Bellvitge-ICO L'Hospitalet, Spain; E-Mail: 35078jbe@comb.cat (J.B.)
2          Group of Neuroplasticity and Regeneration, CIBERNED, Institute of Neuroscience and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barelona, Spain
Abstract:
Taxane-derived agents are a type of chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on their ability to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often as painful neuropathy, experienced during the treatment and  sometimes irreversibly. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior the initiation of treatment.  Present review tries to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with taxane-induced neuropathy development.

Type of paper: Article
Title:
Neurotoxic Effects of Platinum Compounds: Studies in vivo on Central Nervous System
Authors:
G. Bernocchi, F.P. Fanizzi, S.A. De Pascali, V. Insolia, V.M. Piccolini and M.G. Bottone
Affiliations:
1 Dipartimento di Biologia e Biotecnologie "L. Spallanzani" Università di Pavia, via Ferrata 9, 27100, Pavia, Italy
2 Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Salento University, Lecce, Italy
Abstract:
Platinum compounds are known to cause significant clinical neurotoxicity. Several studies highlight neurological complications especially in paediatric oncology patients with CNS and non-CNS malignancies.
To understand the toxicity mechanisms of platinum drugs at cellular and molecular levels in the immature brain, which is much more vulnerable to injury than the adult one, we compared the effects in vivo of the most used platinum compound, i.e., cisdichlorodiammineplatinum (cisplatin, cisPt), with that of a new platinum compound [Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS). As models of developing brain areas we have chosen  the hippocampus gyrus dentatus and cerebellum. Both areas show the events of the neurogenesis process, from proliferation to differentiation and formation of synaptic contacts, and therefore permit to compare the action of platinum compounds with different target, e.g., on DNA and non-DNA target. Here we focused the localization and identification of changes in the intracellular calcium within CNS architecture. At this purpose, we used two immunohistochemical markers of calcium homeostasis system, the calcium buffer protein Calbindin (CB) and Plasma Membrane Calcium ATPase (PMCA1).
From the comparison of the cisPt and PtAcacDMS effects it emerges how essential is the equilibrium and synergy between CB and PMCA1 to warrant the morphology and function of nervous tissue and limit neuroarchitecture damages, obviously depending by the peculiar and intrinsic properties of the developing CNS areas.

Last update: 9 February 2015

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