Role of Aryl Hydrocarbon Receptor and Oxidative Stress in the Regioselective Toxicities of Hydroxychrysenes in Embryonic Japanese Medaka (Oryzias latipes)

Philip Tanabe; Daniel Schlenk

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Role of Aryl Hydrocarbon Receptor and Oxidative Stress in the Regioselective Toxicities of Hydroxychrysenes in Embryonic Japanese Medaka (Oryzias latipes)

机译：Role of Aryl Hydrocarbon Receptor and Oxidative Stress in the Regioselective Toxicities of Hydroxychrysenes in Embryonic Japanese Medaka (Oryzias latipes)

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Oxygenated polycyclic aromatic hydrocarbons (oxy‐PAHs) are environmental contaminants that can be createdthrough oxidation of parent PAHs. Previous studies have found that 2‐hydroxychrysene (2‐OHCHR) caused anemia in embryonicJapanese medaka whereas 6‐hydroxychrysene (6‐OHCHR) did not, an example of regioselective toxicity. Anemia was preventedby cytochrome P450 (CYP) inhibition, which reduced the formation of the potential oxidatively active metabolite, 1,2‐catechol,from 2‐OHCHR. 2‐OHCHR has also been found to be a four‐fold more potent aryl hydrocarbon receptor (AhR) agonist comparedwith 6‐OHCHR. These findings led us to hypothesize that AhR activation and/or oxidative stress play an important role in2‐OHCHR toxicity. Although treatments with the AhR agonists polychlorinated biphenyl (PCB)126 and 2‐methoxychrysene(2‐MeOCHR) did not cause significant toxicity, pretreatments with the AhR antagonist, CH‐223191, reduced anemia by97.2 ± 0.84% and mortality by 96.6 ± 0.69%. Aryl hydrocarbon receptor inhibition by the antagonist was confirmed by significantreductions (91.0 ± 9.94%) in induced ethoxyresorufin‐O‐deethylase activity. Thiobarbituric acid reactive substances concentrationswere 32.9 ± 3.56% higher (p < 0.05) in 2‐OHCHR treatments at 100 hours postfertilization compared with controls.Staining 2‐OHCHR‐treated embryos with the reactive oxygen species (ROS) scavenger 2′,7′‐dichlorofluorescin diacetate revealed32.6 ± 2.69% of 2‐OHCHR‐treated embryos exhibiting high concentrations of ROS in caudal tissues, which is a site for embryonichematopoiesis in medaka. Pretreatment with antioxidants, N‐acetylcysteine (NAC) or vitamin E (Vit E) significantly reduced2‐OHCHR‐induced anemia (NAC: 80.7 ± 1.12% and Vit E: 99.1 ± 0.43%) and mortality (NAC: 67.1 ± 1.69% and Vit E:98.9 ± 0.66%). These results indicate that AhR may mediate 2‐OHCHR toxicity through canonical signaling by up‐regulatingCYP1, enhancing the formation of reactive metabolites of 2‐OHCHR that generate ROS within caudal hematopoietic tissues,potentially disrupting hematopoiesis, leading to anemia and subsequent mortality.

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《Environmental toxicology and chemistry /》 |2023年第3期|698-706|共9页
作者
Philip Tanabe; Daniel Schlenk;
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作者单位

Environmental Toxicology Graduate Program, University of California, Riverside, California, USA Department of Environmental Sciences, University of California, Riverside, California, USA;

Department of Environmental Sciences, University of California, Riverside, California, USA;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
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Aquatic toxicology; Developmental toxicity; Hydroxy‐PAH; Japanese medaka; Mode of action; Oxy‐PAH; Polycyclic aromatic hydrocarbons (PAHs);

Role of Aryl Hydrocarbon Receptor and Oxidative Stress in the Regioselective Toxicities of Hydroxychrysenes in Embryonic Japanese Medaka (Oryzias latipes)

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