Browsing by Author "Pandelides, Zacharias"

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The anti-estrogenic and liver metabolic effects of DHAA in rainbow trout (oncorhynchus mykiss)
(2011-08-01) Pandelides, Zacharias; Holdway, Douglas
Recent studies have shown that dehydroabietic acid (DHAA), a resin acid present in pulp and paper mills, may have anti-estrogenic effects in fish. A chronic-exposure toxicity experiment using immature rainbow trout (Oncorhynchus mykiss) was conducted in order to assess the endocrine disrupting and liver metabolic effects of the wood extractives DHAA and β- sitosterol (BS) regularly present in pulp and paper mills and the model estrogen 17β-estradiol (E2). It was found that exposure to 5 ppm of E2 significantly increased hepatosomatic index (HSI), vitellogenin (VTG) and plasma sorbitol dehydrogenase (SDH). This effect was reduced by mixing E2 with DHAA, indicating that DHAA does not cause its anti-estrogenic effects indirectly due to liver damage. Exposure to 5 ppm of DHAA caused a significant increase in liver citrate synthase (CS), and liver ethoxyresorufin-O-deethylase (EROD) activity after 7 days, however, the fish recovered by 28 days. This study also determined the effect of 14 different pulp and paper mill effluent extracts on liver enzyme metabolism through alterations in the activity of liver lactate dehydrogenase activity (LDH) and CS. This activity varied greatly between mills but most showed an induction of CS after 28 days exposure through i.p. injection. The results of the study indicate that DHAA may alter energy metabolism as well as cause anti-estrogenic effects in female juvenile rainbow trout.
Examining swim bladder inflation failure as a toxicological endpoint in Japanese medaka (Oryzias latipes)
(2017-11-01) Pandelides, Zacharias; Holdway, Douglas
Inadequate swim bladder inflation, while not being lethal itself, can have serious long-term effects on fish populations. Many environmental contaminants can inhibit swim bladder inflation of larval fish. Understanding how swim bladder inflation failure due to pollutant exposure occurs and developing biomarkers for this effect is important. This study demonstrated that embryonic exposure to the pharmaceuticals 17α-ethinylestradiol, levonorgestrel, and diclofenac, impaired swim bladder inflation of Japanese medaka (Oryzias latipes). After exposure to individual compounds, mixture exposures to no-observed-effect concentrations of these compounds were conducted. Significant effects on swim bladder inflation were observed for a binary mixture of 17α-ethinylestradiol, and levonorgestrel, as well as in a mixture of all the compounds. These compounds thus have the potential for significant mixture effects below their individual no-observed-effect concentrations. Many factors associated with swim bladder formation and inflation were investigated. The temporal requirement for an air-water interface for successful swim bladder inflation was determined to be ~5 days for Japanese medaka. Swim bladder inflation failure of medaka larvae was shown to be strongly correlated with decreased survival 12 days post-hatch. This implies that compounds that can disrupt swim bladder inflation of hatched larvae such as those studied in this experiment, may lead to increased mortality of larval fish. Embryonic exposure to 5 μM cyclopamine, a Hedgehog (Hh) signaling inhibitor, as well as 1 μM IWR-1, a Wnt signalling inhibitor, resulted in >95% inhibition of swim bladder inflation of Japanese medaka larvae. The effects of these inhibitors on the expression of medaka genes related to the Hh and Wnt pathways, as well as genes involved in the formation of the three cell layers that make up the swim bladder (epithelial, mesenchyme, and outer mesothelium) were also determined at 80, 96, 101, 144, 180, and 216 hours post fertilization. Effects on expression of key genes related to swim bladder formation and inflation following exposure to 17α-ethinylestradiol, levonorgestrel, and diclofenac were determined. The effects on gene expression of these three pharmaceuticals when compared to those of select signalling pathway inhibitors were more closely related to effects on the wnt pathway than the Hh pathway. These pharmaceutical compounds significantly inhibited the expression of genes related to the formation of the three layers of the swim bladder, with levonorgestrel affecting the most genes tested. While all of the effects observed in this dissertation were caused by concentrations of pharmaceuticals generally above those found in the environment, this study demonstrated that pharmaceutical compounds have the potential to affect medaka embryo development as well as swim bladder inflation.