Cadmium-Benzo[a]pyrene mixture toxicity effects in adult zebrafish (Danio rerio)
Date
2024-01-04
Authors
Journal Title
Journal ISSN
Volume Title
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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
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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