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

Abstract

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.

Expression of aryl hydrocarbon receptor–regulated genes and superoxide dismutase in the Antarctic eelpout Pachycara brachycephalum exposed to benzo[a]pyrene

“…This alteration in gene expression was followed by alterations in the respective metabolic enzyme capacities. In BaP-exposed O. mykiss, changes in the expression of CYP1A were paralleled by the formation of BaP metabolites and therefore are suggested to mirror the response of the xenobiotic metabolism in this species [37]. Accordingly, our findings on the increased expression of both AhR and CYP1A, which remains elevated at least 10 d after injecting BaP, reflect that it might take a longer time to biotransform xenobiotics in Antarctic eelpout compared with temperate species.…”

“…This alteration in gene expression was followed by alterations in the respective metabolic enzyme capacities. In BaP‐exposed O. mykiss , changes in the expression of CYP1A were paralleled by the formation of BaP metabolites and therefore are suggested to mirror the response of the xenobiotic metabolism in this species .…”

“…In zebrafish embryos, waterborne exposure with 50 mg/mL of the AhR agonist b-naphtoflavone caused a 2-fold induction of AhR2, which then resulted in a 200-fold change in CYP1A [46]. Another example of BaP-treated hepatocytes of O. mykiss reported a significant, approximately 2-to 3-fold induction of AhR2 gene expression that was followed by a highly induced expression of CYP1A [37]. Several other studies on temperate fish species further support an induction of CYP1A expression in response to AhR agonists [6,20,47].…”

Polyaromatic hydrocarbons in aquafeeds, source, effects and potential implications for vitamin status of farmed fish species: a review

“…Moller et al . ). Studies on dietary PAH exposures are limited, especially concerning PAH and vitamin effects in the intestine, which is the first barrier for dietary PAH exposure, vitamin uptake and vitamin conversion.…”

Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China — A comprehensive perspective

“…PAHs and phenols have been shown to suppress non-specific cytotoxic cells in teleosts, which are relevant in the immunologic defense from xenogenic targets, like certain fish parasites (Faisal et al, 1991;Graves et al, 1985;Reynaud and Deschaux, 2006;Seeley and Weeks-Perkins, 1997;Taysse et al, 1998). Beyond, Möller et al (2014) demonstrated that PAHs are distributed into the immune organs head kidney and spleen in fish, and that those possess the capability to metabolize PAHs to potentially immunotoxic metabolites, which in their turn may diminish immunological responses (Khan and Thulin, 1991). Further, an increased pollution of the water with organic material can cause an increased reproduction of macroinvertebrates that can serve as intermediate hosts.…”