Cardiovascular and metabolic effects of dietary selenomethionine exposure in fishes
Date
2018-03-22
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0000-0002-8913-7243
Type
Thesis
Degree Level
Masters
Abstract
Selenium (Se) is an essential micronutrient involved in important metabolic functions for all vertebrate species. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Recent studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can alter aerobic metabolic capacity, energetics and swimming performance. My thesis aimed to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in adult zebrafish (Danio rerio) and juvenile (yearling) rainbow trout (Oncorhynchus mykiss). In my first experiment, adult zebrafish were fed either control food (1.1 μg Se/g dry mass [d.m.]) or Se-Met spiked food (10.3 or 28.8 μg Se/g d.m.) for 90 d at 5% body weight per day. In the second experiment, juvenile rainbow trout were fed either control food (1.3 μg Se/g d.m.) or Se-Met spiked food (6.4, 15.8 or 47.8 μg Se/g d.m.) for 60 d at 5% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function. Chronic dietary exposure to elevated Se-Met had opposing results in zebrafish when compared to the rainbow trout. Zebrafish exposed to the highest dietary concentrations of Se-Met (28.8 μg Se/g d.m.) had significantly reduced ventricular contractile rate, stroke volume, and cardiac output, while Se-Met exposed rainbow trout had significantly greater stroke volume, ejection fraction, and cardiac output.
Following ultasonography, energy stores were measured via whole body (zebrafish) and liver, heart and muscle (rainbow trout) glycogen and triglyceride concentrations. Zebrafish in the highest exposure group were observed to have greater whole body glycogen concentrations when compared to the control group, while rainbow trout exposed to Se-Met concentrations greater than 15.8 μg Se/g showed significant increases in both glycogen and triglycerides in liver relative to the control group. In addition, rainbow trout in the highest exposure group had significantly reduced capability of managing blood glucose levels as was evident after 48hrs in a glucose tolerance test.
Exposure to Se-Met significantly decreased mRNA expression of a key cardiac remodelling enzyme, matrix metalloproteinase 2 (MMP2), in adult zebrafish heart, however significantly increased it (MMP9) in rainbow trout heart. Selenomethionine significantly increased echodensity at the junction between atrium and ventricle in zebrafish, and these results combined with increased MMP2 expression are consistent with cardiac remodelling and fibrosis. However, rainbow trout did not show any fibrosis and also had a significant decrease in SERPINH mRNA abundance, a molecular chaperone essential for the post-translational folding of fibril-forming collagens. This, taken together with the increase in MMP9, suggests an anti-fibrotic response in the rainbow trout heart, compared to the fibrosis seen in the zebrafish, which could help explain why there were opposing cardiovascular results. Due to the anti-fibrotic response in rainbow trout, the heart was apparently able to pump blood more effectively leading to the increase in stroke volume, ejection fraction, and cardiac output observed.
The results of this study suggest that chronic exposure to dietary Se-Met can impact cardiac function, energy homeostasis and cause cellular perturbations, and such physiological consequences could reduce the aerobic capacity and survivability of fish. The varying results seen could be attributed to species sensitivity differences or perhaps due to the cold vs warm water fish selenium sensitivity.
Description
Keywords
cardiometabolic, toxicity, selenium,
Citation
Degree
Master of Science (M.Sc.)
Department
Toxicology Centre
Program
Toxicology