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Anthracene is a highly toxic polycyclic aromatic hydrocarbon (PAH), and its toxicity is increased 8-fold after compounding exposure to UV radiation. Exposure to either the parent or photo-modified compound has been shown to cause increases in reactive oxygen species (ROS) production and lipid peroxidation. Since the majority of ROS production occurs within mitochondria, we investigated simultaneous mitochondrial respiration and ROS production in the gills of sheepshead minnows (Cyprinodon variegatus) acutely (48 h) exposed to anthraquinone (40 μg l−1). Anthraquinone exposure caused a 25% increase in oxidative phosphorylation with electrons donated to Complex I (OXPHOS CI) and a 33% increase in Leak respiration with oligomycin (Leak-Omy CI). ROS production was slightly increased (33.3%) in Leak state with oligomyocin respiring on Complex I substrates (Leak-Omy CI) after anthraquinone exposure, but this value remained unchanged in all other respiratory states. When ROS production was normalized to mitochondrial oxygen consumption, we found that ROS production was decreased in all respiratory states, but most noticeably in the Leak state. We speculate that differences in the antioxidant defense system may have played a role in decreased ROS production. Overall, in this paper we present a novel technique to measure mitochondrial function in the gill filaments of teleost fish exposed to xenobiotic molecules, and we show anthraquinone exposure alters aspects of oxidative phosphorylation and ROS production. Unlabelled Image • Novel gill filament preparation to measure mitochondrial respiration and ros production. • Acute anthraquinone exposure increases respiration in oxphos and leak states. • Acute anthraquinone exposures decrease relative ros production in leak states. • Observed results may be evidence of mounting antioxidant defense response to xenobiotic molecules. [ABSTRACT FROM AUTHOR]

Mitochondrial bioenergetics profiling, a measure of oxygen consumption rates, correlates with prognostic markers and can be used to assess response to therapy in chronic lymphocytic leukemia (CLL) cells. In this study, we measured mitochondrial respiration rates in primary CLL cells using respirometry to evaluate mitochondrial function. We found significant increases in mitochondrial respiration rates in CLL versus control B lymphocytes. We also observed amongst CLL patients that advanced age, female sex, zeta-chain-associated protein of 70 kD (ZAP-70+), cluster of differentiation 38 (CD38+), and elevated β2-microglobulin (β2-M) predicted increased maximal respiration rates. ZAP-70+ CLL cells exhibited significantly higher bioenergetics than B lymphocytes or ZAP-70− CLL cells and were more sensitive to the uncoupler, carbonyl cyanide-p-trifluoro-methoxyphenylhydrazone (FCCP). Univariable and multivariable linear regression analysis demonstrated that ZAP-70+ predicted increased maximal respiration. ZAP-70+ is a surrogate for B cell receptor (BCR) activation and can be targeted by ibrutinib, which is a clinically approved Bruton's tyrosine kinase (BTK) inhibitor. Therefore, we evaluated the oxygen consumption rates (OCR) of CLL cells and plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4) levels from ibrutinib-treated patients and demonstrated decreased OCR similar to control B lymphocytes, suggesting that ibrutinib treatment resets the mitochondrial bioenergetics, while diminished CCL3/CCL4 levels indicate the down regulation of the BCR signaling pathway in CLL. Our data support evaluation of mitochondrial respiration as a preclinical tool for the response assessment of CLL cells. [ABSTRACT FROM AUTHOR]