Antagonistic cytoprotective effects of C60 fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model

Michael N. Moore; Susanna Sforzini; Aldo Viarengo; Audrey Barranger; Yann Aminot; James W. Readman; Andrei N. Khlobystov; Volker M. Arlt; Mohamed Banni; Awadhesh N. Jha

doi:10.1016/j.scitotenv.2020.142355

Antagonistic cytoprotective effects of C₆₀ fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model

Michael N. Moore^*, Susanna Sforzini, Aldo Viarengo, Audrey Barranger, Yann Aminot, James W. Readman, Andrei N. Khlobystov, Volker M. Arlt, Mohamed Banni, Awadhesh N. Jha

^*Corresponding author for this work

Genetic & Environmental Toxicology

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The hypothesis that C₆₀ fullerene nanoparticles (C₆₀) exert an antagonistic interactive effect on the toxicity of benzo[a]pyrene (BaP) has been supported by this investigation. Mussels were exposed to BaP (5, 50 & 100 μg/L) and C₆₀ (C₆₀–1 mg/L) separately and in combination. Both BaP and C₆₀ were shown to co-localize in the secondary lysosomes of the hepatopancreatic digestive cells in the digestive gland where they reduced lysosomal membrane stability (LMS) or increased membrane permeability, while BaP also induced increased lysosomal lipid and lipofuscin, indicative of oxidative cell injury and autophagic dysfunction. Combinations of BaP and C₆₀ showed antagonistic effects for lysosomal stability, mTORC1 (mechanistic target of rapamycin complex 1) inhibition and intralysosomal lipid (5 & 50 μg/L BaP). The biomarker data (i.e., LMS, lysosomal lipidosis and lipofuscin accumulation; lysosomal/cell volume and dephosphorylation of mTORC1) were further analysed using multivariate statistics. Principal component and cluster analysis clearly indicated that BaP on its own was more injurious than in combination with C₆₀. Use of a network model that integrated the biomarker data for the cell pathophysiological processes, indicated that there were significant antagonistic interactions in network complexity (% connectance) at all BaP concentrations for the combined treatments. Loss of lysosomal membrane stability probably causes the release of intralysosomal iron and hydrolases into the cytosol, where iron can generate harmful reactive oxygen species (ROS). It was inferred that this adverse oxidative reaction induced by BaP was ameliorated in the combination treatments by the ROS scavenging property of intralysosomal C₆₀, thus limiting the injury to the lysosomal membrane; and reducing the oxidative damage in the cytosol and to the nuclear DNA. The ROS scavenging by C₆₀, in combination with enhanced autophagic turnover of damaged cell constituents, appeared to have a cytoprotective effect against the toxic reaction to BaP in the combined treatments.

Original language	English
Article number	142355
Journal	Science of the Total Environment
Volume	755
DOIs	https://doi.org/10.1016/j.scitotenv.2020.142355
Publication status	Published - 10 Feb 2021

Keywords

Antagonism
Autophagy
C-nanoparticles
Complexity
Lysosomes
Oxidative-injury

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10.1016/j.scitotenv.2020.142355

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Moore, M. N., Sforzini, S., Viarengo, A., Barranger, A., Aminot, Y., Readman, J. W., Khlobystov, A. N., Arlt, V. M., Banni, M., & Jha, A. N. (2021). Antagonistic cytoprotective effects of C₆₀ fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model. Science of the Total Environment, 755, Article 142355. https://doi.org/10.1016/j.scitotenv.2020.142355

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title = "Antagonistic cytoprotective effects of C60 fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model",

abstract = "The hypothesis that C60 fullerene nanoparticles (C60) exert an antagonistic interactive effect on the toxicity of benzo[a]pyrene (BaP) has been supported by this investigation. Mussels were exposed to BaP (5, 50 & 100 μg/L) and C60 (C60–1 mg/L) separately and in combination. Both BaP and C60 were shown to co-localize in the secondary lysosomes of the hepatopancreatic digestive cells in the digestive gland where they reduced lysosomal membrane stability (LMS) or increased membrane permeability, while BaP also induced increased lysosomal lipid and lipofuscin, indicative of oxidative cell injury and autophagic dysfunction. Combinations of BaP and C60 showed antagonistic effects for lysosomal stability, mTORC1 (mechanistic target of rapamycin complex 1) inhibition and intralysosomal lipid (5 & 50 μg/L BaP). The biomarker data (i.e., LMS, lysosomal lipidosis and lipofuscin accumulation; lysosomal/cell volume and dephosphorylation of mTORC1) were further analysed using multivariate statistics. Principal component and cluster analysis clearly indicated that BaP on its own was more injurious than in combination with C60. Use of a network model that integrated the biomarker data for the cell pathophysiological processes, indicated that there were significant antagonistic interactions in network complexity (% connectance) at all BaP concentrations for the combined treatments. Loss of lysosomal membrane stability probably causes the release of intralysosomal iron and hydrolases into the cytosol, where iron can generate harmful reactive oxygen species (ROS). It was inferred that this adverse oxidative reaction induced by BaP was ameliorated in the combination treatments by the ROS scavenging property of intralysosomal C60, thus limiting the injury to the lysosomal membrane; and reducing the oxidative damage in the cytosol and to the nuclear DNA. The ROS scavenging by C60, in combination with enhanced autophagic turnover of damaged cell constituents, appeared to have a cytoprotective effect against the toxic reaction to BaP in the combined treatments.",

keywords = "Antagonism, Autophagy, C-nanoparticles, Complexity, Lysosomes, Oxidative-injury",

author = "Moore, {Michael N.} and Susanna Sforzini and Aldo Viarengo and Audrey Barranger and Yann Aminot and Readman, {James W.} and Khlobystov, {Andrei N.} and Arlt, {Volker M.} and Mohamed Banni and Jha, {Awadhesh N.}",

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T1 - Antagonistic cytoprotective effects of C60 fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model

AU - Moore, Michael N.

AU - Sforzini, Susanna

AU - Viarengo, Aldo

AU - Barranger, Audrey

AU - Aminot, Yann

AU - Readman, James W.

AU - Khlobystov, Andrei N.

AU - Arlt, Volker M.

AU - Banni, Mohamed

AU - Jha, Awadhesh N.

PY - 2021/2/10

Y1 - 2021/2/10

N2 - The hypothesis that C60 fullerene nanoparticles (C60) exert an antagonistic interactive effect on the toxicity of benzo[a]pyrene (BaP) has been supported by this investigation. Mussels were exposed to BaP (5, 50 & 100 μg/L) and C60 (C60–1 mg/L) separately and in combination. Both BaP and C60 were shown to co-localize in the secondary lysosomes of the hepatopancreatic digestive cells in the digestive gland where they reduced lysosomal membrane stability (LMS) or increased membrane permeability, while BaP also induced increased lysosomal lipid and lipofuscin, indicative of oxidative cell injury and autophagic dysfunction. Combinations of BaP and C60 showed antagonistic effects for lysosomal stability, mTORC1 (mechanistic target of rapamycin complex 1) inhibition and intralysosomal lipid (5 & 50 μg/L BaP). The biomarker data (i.e., LMS, lysosomal lipidosis and lipofuscin accumulation; lysosomal/cell volume and dephosphorylation of mTORC1) were further analysed using multivariate statistics. Principal component and cluster analysis clearly indicated that BaP on its own was more injurious than in combination with C60. Use of a network model that integrated the biomarker data for the cell pathophysiological processes, indicated that there were significant antagonistic interactions in network complexity (% connectance) at all BaP concentrations for the combined treatments. Loss of lysosomal membrane stability probably causes the release of intralysosomal iron and hydrolases into the cytosol, where iron can generate harmful reactive oxygen species (ROS). It was inferred that this adverse oxidative reaction induced by BaP was ameliorated in the combination treatments by the ROS scavenging property of intralysosomal C60, thus limiting the injury to the lysosomal membrane; and reducing the oxidative damage in the cytosol and to the nuclear DNA. The ROS scavenging by C60, in combination with enhanced autophagic turnover of damaged cell constituents, appeared to have a cytoprotective effect against the toxic reaction to BaP in the combined treatments.

AB - The hypothesis that C60 fullerene nanoparticles (C60) exert an antagonistic interactive effect on the toxicity of benzo[a]pyrene (BaP) has been supported by this investigation. Mussels were exposed to BaP (5, 50 & 100 μg/L) and C60 (C60–1 mg/L) separately and in combination. Both BaP and C60 were shown to co-localize in the secondary lysosomes of the hepatopancreatic digestive cells in the digestive gland where they reduced lysosomal membrane stability (LMS) or increased membrane permeability, while BaP also induced increased lysosomal lipid and lipofuscin, indicative of oxidative cell injury and autophagic dysfunction. Combinations of BaP and C60 showed antagonistic effects for lysosomal stability, mTORC1 (mechanistic target of rapamycin complex 1) inhibition and intralysosomal lipid (5 & 50 μg/L BaP). The biomarker data (i.e., LMS, lysosomal lipidosis and lipofuscin accumulation; lysosomal/cell volume and dephosphorylation of mTORC1) were further analysed using multivariate statistics. Principal component and cluster analysis clearly indicated that BaP on its own was more injurious than in combination with C60. Use of a network model that integrated the biomarker data for the cell pathophysiological processes, indicated that there were significant antagonistic interactions in network complexity (% connectance) at all BaP concentrations for the combined treatments. Loss of lysosomal membrane stability probably causes the release of intralysosomal iron and hydrolases into the cytosol, where iron can generate harmful reactive oxygen species (ROS). It was inferred that this adverse oxidative reaction induced by BaP was ameliorated in the combination treatments by the ROS scavenging property of intralysosomal C60, thus limiting the injury to the lysosomal membrane; and reducing the oxidative damage in the cytosol and to the nuclear DNA. The ROS scavenging by C60, in combination with enhanced autophagic turnover of damaged cell constituents, appeared to have a cytoprotective effect against the toxic reaction to BaP in the combined treatments.

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KW - Autophagy

KW - C-nanoparticles

KW - Complexity

KW - Lysosomes

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Antagonistic cytoprotective effects of C₆₀ fullerene nanoparticles in simultaneous exposure to benzo[a]pyrene in a molluscan animal model

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Keywords

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