Comparative in vitro metabolism of benzo[a]pyrene by recombinant zebrafish CYP1A and liver microsomes from β-naphthoflavone-treated rainbow trout

Miranda, Cristobal L.; Chung, Won Gyun; Wang-Buhler, Jun-Lan; Musafia-Jeknic, Tamara; Baird, William M.; Buhler, Donald R.

doi:10.1016/j.aquatox.2006.07.018

Cited by 35 publications

(22 citation statements)

References 44 publications

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“…Nonproduction of BaP-4,5-diol by fish tissues was reported by other authors as well (Stegeman et al, 1984;Yuan et al, 1997). Miranda et al (2006) suggested that BaP-4,5-diol might be detectable in microsomal preparations only if huge amounts of microsomes are used and the products are concentrated before HPLC analysis.…”

Section: Discussionmentioning

confidence: 96%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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Polycyclic aromatic hydrocarbons (PAHs) are immunotoxicants in fish. In mammals, phase I metabolites are believed to be critically involved in the immunotoxicity of PAHs. This mechanism has been suggested for fish as well. The present study investigates the capacity of immune organs (head kidney, spleen) of rainbow trout, Oncorhynchus mykiss, to metabolize the prototypic PAH, benzo [a]pyrene (BaP). To this end, we analyzed 1) the induction of enzymatic capacity measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in immune organs compared with liver, 2) the organ profiles of BaP metabolites generated in vivo, and 3) rates of microsomal BaP metabolite production in vitro. All measurements were done for control fish and for fish treated with an intraperitoneal injection of 15 mg BaP/kg body weight. In exposed trout, the liver, head kidney, and spleen contained similar levels of BaP, whereas EROD induction differed significantly between the organs, with liver showing the highest induction factor (132.83), followed by head kidney (38.43) and spleen (1.43). Likewise, rates of microsomal metabolite formation experienced the highest induction in the liver of BaP-exposed trout, followed by the head kidney and spleen. Microsomes from control fish displayed tissue-specific differences in metabolite production. In contrast, in BaP-exposed trout, microsomes of all organs produced the potentially immunotoxic BaP-7,8-dihydrodiol as the main metabolite. The findings from this study show that PAHs, like BaP, are distributed into immune organs of fish and provide the first evidence that immune organs possess inducible PAH metabolism leading to in situ production of potentially immunotoxic PAH metabolites.

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Section: Discussionmentioning

confidence: 96%

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

et al. 2013

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“…BaP is a known agonist of the aryl hydrocarbon receptor (AhR) and causes induction of several biotransformation enzymes (Buhler and Williams, 1989;Miller and Ramos, 2001;Miranda et al, 2006). It is these enzymes, mainly phase one cytochrome P4501A (CYP1A) isoforms, which are responsible for the biotransformation of BaP to reactive metabolites.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the acute effects of benzo-a-pyrene on adult zebrafish (Danio rerio) cardiorespiratory function following intraperitoneal injection versus aqueous exposure

Gerger

Weber

2015

Aquatic Toxicology

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“…Binding of a ligand, such as a PAH, to the AHR results in up-regulation of numerous downstream genes, including the cytochrome P450s ( cyp genes), which metabolize certain AHR ligands, including PAHs (Denison and Nagy, 2003; Miranda et al , 2006; Schmidt and Bradfield, 1996). …”

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confidence: 99%

Mechanistic Investigations Into the Developmental Toxicity of Nitrated and Heterocyclic PAHs

Chlebowski

Garcia

et al. 2017

Toxicological Sciences

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Nitrated polycyclic aromatic hydrocarbons (NPAHs) and heterocyclic PAHs (HPAHs) are recognized environmental pollutants. However, the health risks of NPAHs and HPAHs to humans and environmental systems are not well-studied. The developmental zebrafish (Danio rerio) model was used to evaluate the toxicity of a structurally diverse set of 27 NPAHs and 10 HPAHs. The individual activity of each compound towards the aryl hydrocarbon receptor (AHR), including the role of the AHR in observed toxicity, and genetic markers of oxidative stress and cardiac toxicity were evaluated. Zebrafish embryos were exposed from 6 to 120 hours post fertilization (hpf), to a broad concentration range of individual compounds, and evaluated for 22 developmental endpoints. The potential role of AHR was determined using the transgenic Tg(cyp1a:nls-egfp) reporter zebrafish line. All compounds were screened computationally through molecular docking using a previously developed AHR models of zebrafish isoforms 1A, 1B, and 2. Some compounds did not induce observable developmental toxic responses, whereas others produced statistically significant concentration-dependent toxicity. The tested compounds also exhibited a range of predicted AHR binding and cyp1a/GFP induction patterns, including cyp1a expression in the liver, vasculature, skin, and yolk, which we determined to be due to distinct isoforms of the AHR, using morpholino oligonucleotide knockdown. Furthermore, we investigated mRNA expression of oxidative and cardiac stress genes at 48 and 120 hpf, which indicated several potential mechanisms-of-action for NPAHs. Overall, we observed a range of developmental toxicities, cyp1a/GFP expression patterns, and gene expression profiles, suggestive of several potential mechanisms of action.

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Comparative in vitro metabolism of benzo[a]pyrene by recombinant zebrafish CYP1A and liver microsomes from β-naphthoflavone-treated rainbow trout

Cited by 35 publications

References 44 publications

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Tissue-Specific Metabolism of Benzo[a]pyrene in Rainbow Trout (Oncorhynchus mykiss): A Comparison between the Liver and Immune Organs

Comparison of the acute effects of benzo-a-pyrene on adult zebrafish (Danio rerio) cardiorespiratory function following intraperitoneal injection versus aqueous exposure

Mechanistic Investigations Into the Developmental Toxicity of Nitrated and Heterocyclic PAHs

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