Yeh 2017 Aquat Toxicol

Yeh A, Marcinek DJ, Meador JP, Gallagher EP (2017) Effect of contaminants of emerging concern on liver mitochondrial function in Chinook salmon. Aquat Toxicol 190:21-31.

» PMID: 28668760

Yeh A, Marcinek DJ, Meador JP, Gallagher EP (2017) Aquat Toxicol

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) Y 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). 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.

Copyright © 2017 Elsevier B.V. All rights reserved. • Keywords: Chinook salmon, Contaminants of emerging concern, Mitochondria, Oxidative stress • Bioblast editor: Kandolf G • O2k-Network Lab: US WA Seattle Kushmerick MJ, US WA Seattle Marcinek DJ

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology 

Organism: Fishes  Tissue;cell: Liver  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2017-09