Organ-specific manganese toxicity: a comparative in vitro study on five cellular models exposed to MnCl2

Rovetta, Francesca; Catalani, Simona; Steimberg, Nathalie; Boniotti, Jennifer; Gilberti, Maria Enrica; Mariggiò, Maria Addolorata; Mazzoleni, Giovanna

doi:10.1016/j.tiv.2006.08.010

Cited by 27 publications

(18 citation statements)

References 22 publications

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“…Results from these viability experiments showed that neurons are more sensitive to cytotoxic effects of agents tested in all cases excepting for GF, which induces similar cytotoxicity in both cell types. This agrees with previous studies generally showing more sensitivity of neuronal cells to cytotoxicity induction as compared to glial cells (Coccini et al, 2015;Coleman et al, 2002;Rovetta et al, 2007). The relatively higher resistance of A172 cells to toxicity compared with the SH-SY5Y cells reflects to some extent the role of astrocytes in vivo.…”

Section: Discussionsupporting

confidence: 92%

“…Indeed, the diverse response of these cells against the same external insult (Coccini et al, 2015;Coleman et al, 2002), and also the different effects manifested regarding cells from other origins (e.g., hepatocytes, kidney cells, lymphocytes, skeletal muscle cells, etc.) (Rovetta et al, 2007;Valdiglesias et al, 2010) have been previously documented, supporting the relevance of employing particularly nervous system cell types for testing the toxicity of chemicals suspicious of being able to cross the bloodbrain barrier (e.g., nanomaterials). Moreover, most studies found in the literature employed just one of these cell types, restricting the neurotoxicity assessment perspective.…”

Section: Discussionmentioning

confidence: 79%

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Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing

Laffón

Fernández-Bertólez

Costa

et al. 2017

Food and Chemical Toxicology

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a b s t r a c tCell cultures from neuronal and glial origin have proven to be powerful tools for elucidating cellular and molecular mechanisms of nervous system development and physiology, and as neurotoxicity models to evaluate in vitro the possible effects of chemicals. But cellular heterogeneity of nervous system is considerable and these cells have been shown to respond diversely to neurotoxic insults, leading to disparate results from different studies. To shed more light on suitability of cellular models of nervous origin for neurotoxicity screening, the objective of this study was to compare the sensitivity to genetic damage induction of two nervous cell lines. To this aim, neurons (SH-SY5Y) and glial (A172) cells were treated with differently-acting genotoxic agents (bleomycin, actinomycin-D, methyl methanesulfonate, mitomycin C, and griseofulvin). After discarding cytotoxicity, genotoxicity was evaluated by a battery of assays encompassing detection of different genetic lesions. Results obtained showed that glial cells are generally more resistant to genotoxic damage induced by clastogenic agents, but more sensitive to aneugenic effects. These results highlight the need of proper design of in vitro neurotoxicology studies, especially for neurogenotoxicity screening, emphasizing the importance of employing more than one nervous cell type for testing the potential toxicity of a particular exposure.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 79%

Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing

Laffón

Fernández-Bertólez

Costa

et al. 2017

Food and Chemical Toxicology

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“…Here we demonstrate for first time that Mn causes significant damage to the sensory hair cells, peripheral ANF and SGN in cochlear organotypic cultures isolated from postnatal day 3 rats (Figure 2–4) at Mn concentrations comparable to those employed previously to investigate cellular damage in other tissues (Crooks et al, 2007, Rovetta et al, 2007). While the damage seen with our highest Mn concentrations (1–5 mM) could be due to in part to osmotic effects, we believe this is unlikely since this has not been reported in other in vitro studies using high concentration of Mn (Crooks et al, 2007, Rovetta et al, 2007). Moreover, osmotic effects clearly cannot account for the hair cell and neuronal damage seen with micromolar concentrations of Mn.…”

Section: 0 Discussionsupporting

confidence: 66%

Manganese is toxic to spiral ganglion neurons and hair cells in vitro

Ding¹,

Roth

Salvi³

2011

NeuroToxicology

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Occupational exposure to high atmospheric levels of Mn produces a severe and debilitating disorder known as manganism characterized by extrapyramidal disturbances similar to that seen in Parkinson's disease. Epidemiological and case studies suggest that persistent exposures to Mn may have deleterious effects on other organs including the auditory system and hearing. Mn accumulates in the inner ear following acute exposure raising the possibility that it can damage the sensory hair cells that convert sound into neural activity or spiral ganglion neurons (SGN) that transmit acoustic information from the hair cells to the brain via the auditory nerve. In this paper we demonstrate for first time that Mn causes significant damage to the sensory hair cells, peripheral auditory nerve fibers (ANF) and SGN in cochlear organotypic cultures isolated from postnatal day three rats. The peripheral ANF that make synaptic contact with the sensory hair cells were particularly vulnerable to Mn toxicity; damage occurred at concentrations as low 0.01 mM and increased with dose and duration of Mn exposure. Sensory hair cells, in contrast, were slightly more resistant to Mn toxicity than the ANF. Mn induced an atypical pattern of sensory cell damage; Mn was more toxic to inner hair cells (IHC) than outer hair cells (OHC) and in addition, IHC loss was relatively uniform along the length of the cochlea. Mn also caused significant loss and shrinkage of SGN soma. These findings are the first to demonstrate that Mn can produce severe lesions to both neurons and hair cells in the postnatal inner ear.

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“…The threshold of manganese toxicity in vivo is unknown, but the maximal increase in plasma concentration (25 nmol/l) reached in our patients was 4,000 times less than the toxic dose in vitro (36). This explains why we observed no clinical or biological side effects of mangafodipir during the trial.…”

Section: Discussionmentioning

confidence: 53%

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat¹,

Alexandre²,

Nicco³

et al. 2013

J. Clin. Invest.

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Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Funding.

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Organ-specific manganese toxicity: a comparative in vitro study on five cellular models exposed to MnCl2

Cited by 27 publications

References 22 publications

Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing

Comparative study of human neuronal and glial cell sensitivity for in vitro neurogenotoxicity testing

Manganese is toxic to spiral ganglion neurons and hair cells in vitro

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

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