Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon

Abstract

We previously reported the bioaccumulation of contaminants of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) and perfluorinated compounds, in field-collected juvenile Chinook salmon from urban estuaries of Puget Sound, WA (Meador et al., 2016). Although the toxicological impacts of CECs on salmon are poorly understood, several of the detected contaminants disrupt mitochondrial function in other species. Here, we sought to determine whether environmental exposures to CECs are associated with hepatic mitochondrial dysfunction in juvenile Chinook. Fish were exposed in the laboratory to a dietary mixture of 16 analytes representative of the predominant CECs detected in our field study. Liver mitochondrial content was reduced in fish exposed to CECs, which occurred concomitantly with a 24–32% reduction in expression of peroxisome proliferator-activated receptor (PPAR) ϒ coactivator-1a (pgc-1α), a positive transcriptional regulator of mitochondrial biogenesis. The laboratory exposures also caused a 40–70% elevation of state 4 respiration per unit mitochondria, which drove a 29–38% reduction of efficiency of oxidative phosphorylation relative to controls. The mixture-induced elevation of respiration was associated with increased oxidative injury as evidenced by increased mitochondrial protein carbonyls, elevated expression of glutathione (GSH) peroxidase 4 (gpx4), a mitochondrial-associated GSH peroxidase that protects against lipid peroxidation, and reduction of mitochondrial GSH. Juvenile Chinook sampled in a WWTP effluent-impacted estuary with demonstrated releases of CECs showed similar trends toward reduced liver mitochondrial content and elevated respiratory activity per mitochondria (including state 3 and uncoupled respiration). Interestingly, however, respiratory control ratios were greater in fish from the contaminated site relative to fish from a minimally-polluted reference site, which may have been due to differences in the timing of exposure to CECs under laboratory and field conditions. Our results indicate that exposure to CECs can affect both mitochondrial quality and content, and support the analysis of mitochondrial function as an indicator of the sublethal effects of CECs in wild fish.

Metabolomic Investigations of the Temporal Effects of Exposure to Pharmaceuticals and Personal Care Products and Their Mixture in the Eastern Oyster (Crassostrea virginica)

“…This could provide an explanation for the detected decreases in the Krebs cycle metabolites in oysters exposed to diphenhydramine at this time point; however, ATP levels were not quantified in the present study. Supporting this hypothesis, chinook salmon ( Oncorhynchus tshawytscha ) exposed to a chemical mixture (that included both diphenhydramine and fluoxetine) showed increases in liver mitochondria respiration rates and a reduction in total mitochondrial glutathione, suggesting reductions in ATP synthesis, metabolic capacity, and oxidative stress (Yeh et al ).…”

Impact of multiple stressors on juvenile fish in estuaries of the northeast Pacific

“…First, we can minimize or continue to ban contaminants, such as polychlorinated biphenyls (PCBs), that persist in riverine and estuarine food webs years after chemical use is discontinued (e.g., West, O'Neill, & Ylitalo, 2017). In particular, Chinook salmon near wastewater treatment plants accumulate many contaminants of emerging concern (Meador et al, 2016), including some that impair liver mitochondrial function (Yeh, Marcinek, Meador, & Gallagher, 2017 (Lamb et al, 2017;Lotze et al, 2006). Managing water flow is an ongoing challenge in coastal systems worldwide, and maintaining a balance between human needs (e.g., water consumption and diversion; Cloern & Jassby, 2012), and fish health will be key to sustaining coastal ecosystem services.…”

“…PCBs), that persist in riverine and estuarine food webs years after chemical use is discontinued (e.g.,West, O'Neill, & Ylitalo, 2017). In particular, Chinook salmon near wastewater treatment plants accumulate many contaminants of emerging concern(Meador et al, 2016), including some that impair liver mitochondrial function(Yeh, Marcinek, Meador, & Gallagher, 2017). Next, we can conserve or restore biogenic fish habitats (e.g., seagrass meadows, oyster reefs) that maintain water quality for coastal F I G U R E 5 Predicted CPUE, when present, of English sole among estuaries.…”

Emerging Pollutants–Part I: Occurrence, Fate and Transport

“…Personal care products. PPCPs have been widely detected in different ecosystems worldwide and are recognized as contaminants of concern, their environmental toxicology has also been highlighted Based on the microscopic analysis, it was reported that exposure to contaminants of emerging concern can affect both mitochondrial quality and content, particularly in liver, resulting in sublethal effects on wild fish (Yeh et al 2017). The study of Hoobin et al Another study revealed that the mobile genetic elements were abundant in sludge from wastewater treatment plants, which was likely important for the acquisition and mobility of various ARGs among the bacterial species and increased the risk of ARG horizontal transfer (Guo et al 2017).…”