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

Sci Total Environ. 2021 Feb 10;755(Pt 1):142355. doi: 10.1016/j.scitotenv.2020.142355. Epub 2020 Sep 21.

Authors

Affiliations

¹ School of Biological and Marine Sciences, University of Plymouth, Plymouth PL4 8AA, UK; European Centre for Environment & Human Health (ECEHH), University of Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Cornwall TR1 3LJ, UK; Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK. Electronic address: mnm@pml.ac.uk.
² Institute for the Study of Anthropic Impacts and Sustainability in Marine Environment - IAS, National Research Council - CNR, Via de Marini, 6, 16149 Genova, GE, Italy.
³ School of Biological and Marine Sciences, University of Plymouth, Plymouth PL4 8AA, UK.
⁴ School of Biological and Marine Sciences, University of Plymouth, Plymouth PL4 8AA, UK; Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK.
⁵ School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK; Nanoscale and Microscale Research Centre, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
⁶ Department of Analytical, Environmental and Forensic Sciences, King's College London, MRC-PHE Centre for Environmental & Health, London SE1 9NH, UK; Toxicology Department, GAB Consulting GmbH, 69126 Heidelberg, Germany.
⁷ Laboratory of Biochemistry and Environmental Toxicology, ISA, Chott-Mariem, Sousse, Tunisia.

PMID: 33022458
DOI: 10.1016/j.scitotenv.2020.142355

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 & 100μg/L) and C₆₀ (C₆₀-1mg/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 & 50μg/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(60)-nanoparticles; Complexity; Lysosomes; Oxidative-injury.

MeSH terms

Animals
Benzo(a)pyrene / toxicity
Fullerenes* / toxicity
Lysosomes
Models, Animal
Nanoparticles* / toxicity

Substances

Fullerenes
Benzo(a)pyrene