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Cadmium-Benzo[a]pyrene mixture toxicity effects in adult zebrafish (Danio rerio)

Date

2024-01-04

Journal Title

Journal ISSN

Volume Title

Publisher

ORCID

0000-0002-9016-2307

Type

Thesis

Degree Level

Doctoral

Abstract

Environmental water quality guidelines are often established under the assumption that the toxicity of environmental pollutants is identical when present in isolation or in a complex chemical mixture. Thus, there is a crucial gap in our knowledge regarding how these toxicants interact and alter the toxicological effects in aquatic organisms. The present thesis explored how two such ubiquitous toxicants, the trace metal cadmium (Cd) and polycyclic aromatic hydrocarbon Benzo[a]pyrene (BaP), cause interactive toxic effects in adult zebrafish during acute (72 hrs) and sub-chronic (28 day) exposures. Firstly, fish were exposed to either acute (72 hrs) binary mixtures of both toxicants (using 5.8 or 22 μg/L for Cd and 0.44 or 1.07μg/L for BaP), or each toxicant by itself (Chapter 2). Co-exposed animals demonstrated significantly increased tissue accumulation for both toxicants, which did not translate into elevated levels of oxidative stress (as measured by lipid hydroperoxide). Additionally, the mixture caused significant modulation of several detoxification genes, including cytochrome p4501a (CYP1A1) and metallothionein-2 (MT2), superoxide dismutase 1 (SOD1) and catalase (CAT) in the gills. Further experiments aimed to examine the mechanism behind the observed increase in tissue accumulation of both toxicants, by first exposing fish to 10 μg/L Cd and 1 μg/L BaP for 72 hrs, following which toxicant uptake rates were measured using short-term exposures to radiotracers (109Cd and 14C-BaP) (Chapter 3). Cd uptake rate was significantly higher in the gills when animals were pre-exposed to both toxicants simultaneously, resulting in an increased maximum uptake rate (Jmax). The higher Cd uptake was not accompanied by an increase in expression of gill Cd transporters (epithelium calcium channel (ECaC) and the divalent metal transporter 1 (DMT1)). Similarly, whole-body BaP uptake rate increased significantly when cold Cd was added to the 14C-BaP radiotracer exposure, implicating a direct interaction between the two toxicants at the time of uptake. Finally, sub-chronic effects associated iv with the mixture were studied by exposing fish to either 1 or 10 μg/L Cd and 0.1 or 1 μg/L BaP, in isolation or together, for 28 days (Chapter 4). Co-exposed fish showed extensive modulation of several key antioxidant genes (GPx, SOD1, catalase), detoxifying genes (MT1, MT2, CYP1A1) and a stress biomarker (heat-shock protein (HSP70)). Additionally, several cardiotoxic effects were identified in co-exposed animals using ultrasonographic analysis, including a decrease of E-wave peak velocity, end diastolic volume and stroke volume. Overall, the present thesis has identified several sublethal toxic effects caused by aqueous exposures to Cd-BaP mixtures at environmentally relevant concentrations in adult zebrafish (Danio rerio).

Description

Keywords

mixture toxicology

Citation

Degree

Doctor of Philosophy (Ph.D.)

Department

Biology

Program

Biology

Part Of

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DOI

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