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1.
Environ Pollut ; 339: 122731, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37839680

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.


Subject(s)
Caenorhabditis elegans Proteins , Carcinogens, Environmental , Animals , Benzo(a)pyrene/toxicity , Benzo(a)pyrene/metabolism , Caenorhabditis elegans/metabolism , Cytochrome P-450 Enzyme System/metabolism , Cytochrome P-450 CYP1A1/metabolism , Lipids , Mammals/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Vesicular Inhibitory Amino Acid Transport Proteins
2.
Arch Toxicol ; 95(3): 1055-1069, 2021 03.
Article in English | MEDLINE | ID: mdl-33420596

ABSTRACT

Benzo[a]pyrene (BaP) is bioactivated in most organisms by the cytochrome P450 (CYP) enzymes, mainly CYP1A1, ultimately resulting in the reactive metabolite BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) capable of covalently binding to DNA and forming adducts. This step has been defined as the key process in cancer initiation in humans. However, limited knowledge is available about the consequences of BaP exposure in organisms lacking this classical CYP1A1 pathway, one example is the model nematode Caenorhabditis elegans. The aim of this study was to define the genotoxic potential of BaP in C. elegans and to advance our understanding of xenobiotic processing in the absence of the CYP1A1 pathway. Exposure to high concentrations of BaP (0-40 µM) significantly affected life cycle endpoints of C. elegans, which were manifested by a reduced reproductive output and shortened life span. An optimised comet assay revealed that DNA damage increased in a dose-dependent manner; however, no bulky DNA adducts (dG-N2-BPDE) were observed by 32P-postlabelling. Global transcriptomic analysis by RNA-Seq identified responsive transcript families, most prominently members of the cyp-35 and UDP-glucuronosyltransferases (UGTs) enzyme families, both of which are linked to xenobiotic metabolism. Strains harbouring mutations in the cyp-35A2 and cyp-35A3 genes were notably less prone to BaP-mediated toxicity, and BaP led to longevity in cyp-35A5 mutants. In summary, BaP induces transcriptional, genotoxic and phenotypic responses in C. elegans, despite the absence of the classical CYP1A1 bioactivation pathway. This provides first evidence that parallel pathways are implicated in BaP metabolism in C. elegans and this seems to be mediated via the cyp-35 pathway.


Subject(s)
Benzo(a)pyrene/toxicity , Caenorhabditis elegans/drug effects , DNA Damage/drug effects , Mutagens/toxicity , Animals , Benzo(a)pyrene/administration & dosage , Benzo(a)pyrene/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Comet Assay , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 Enzyme System/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Mutagenicity Tests , Mutagens/administration & dosage
3.
Environ Pollut ; 251: 453-459, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31103005

ABSTRACT

Microplastic (MP) pollution is everywhere. In terrestrial environments, microfibres (MFs) generated from textile laundering are believed to form a significant component of MPs entering soils, mainly through sewage sludge and compost applications. The aim of this study was to assess the effect of MFs on a keystone soil organism. We exposed the earthworm Lumbricus terrestris to soil with polyester MFs incorporated at rates of 0, 0.1 and 1.0 %w/w MF for a period of 35 days (in the dark at 15 °C; n = 4 for each treatment). Dried plant litter was applied at the soil surface as a food source for the earthworms. We assessed earthworm vitality through mortality, weight change, depurate production and MF avoidance testing. In addition, we measured stress biomarker responses via the expression of metallothionein-2 (mt-2), heat shock protein (hsp70) and superoxide dismutase (sod-1). Our results showed that exposure and ingestion of MFs (as evidenced by subsequent retrieval of MFs within earthworm depurates) were not lethal to earthworms, nor did earthworms actively avoid MFs. However, earthworms in the MF1.0% treatment showed a 1.5-fold lower cast production, a 24.3-fold increase in expression of mt-2 (p < 0.001) and a 9.9-fold decline in hsp70 expression (p < 0.001). Further analysis of soil and MF samples indicated that metal content was not a contributor to the biomarker results. Given that burrowing and feeding behaviour, as well as molecular genetic biomarkers, were modulated in earthworms exposed to MFs, our study highlights potential implications for soil ecosystem processes due to MF contamination.


Subject(s)
Oligochaeta/drug effects , Plastics/toxicity , Polyesters/toxicity , Soil Pollutants/toxicity , Animals , Behavior, Animal/drug effects , Environmental Biomarkers/drug effects , Environmental Biomarkers/genetics , Oligochaeta/genetics , Oligochaeta/metabolism , Plastics/metabolism , Polyesters/metabolism , Soil Pollutants/metabolism , Stress, Physiological/drug effects , Stress, Physiological/genetics
5.
Asian Pac J Trop Med ; 7S1: S546-52, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25312182

ABSTRACT

OBJECTIVE: To evaluate the antibacterial activity of the extracts of Laurus nobilis against three Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212 and Staphylococcus epidermidis CIP 444) and two Gram-negative bacteria (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853). Also, the antibiofilm activity has been investigated against the biofilm produced by Staphylococcus epidermidis CIP 444. MATERIALS: The polysaccharides, essential oil, and fatty oils extracted from the plant were used in broth microdilution methods to study the minimal inhibitory concentration, and then the minimal bactericidal concentration was determined. RESULTS: The results showed that alginate, fucoidan, fatty oils and essential oil have good antibacterial activities against the 5 bacterial strains, and a negligible biofilm eradication activity of fucoidan, laminaran, fatty oil, and essential oil was observed, but a promising biofilm eradication activity was obtained with alginate, which showed a reduced biofilm mass even at low concentration. CONCLUSIONS: The extracts obtained have promising antibacterial capacities which need further investigation for them to be incorporated in medical or nutritional applications.

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