Subacute nicotine co-exposure has no effect on 2,2′,3,5′,6- pentachlorobiphenyl disposition but alters hepatic cytochrome P450 expression in the male rat

Abstract

Polychlorinated biphenyls (PCBs) are metabolized by cytochrome P450 2B enzymes (CYP2B) and nicotine is reported to alter CYP2B activity in the brain and liver. To test the hypothesis that nicotine influences PCB disposition, 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95) and its metabolites were quantified in tissues of adult male Wistar rats exposed to PCB 95 (6 mg/kg/d, p.o.) in the absence or presence of nicotine (1.0 mg/kg/d of the tartrate salt, s.c.) for 7 consecutive days. PCB 95 was enantioselectively metabolized to hydroxylated (OH-) PCB metabolites, resulting in a pronounced enrichment of E1-PCB 95 in all tissues investigated. OH-PCBs were detected in blood and liver tissue, but were below the detection limit in adipose, brain and muscle tissues. Co-exposure to nicotine did not change PCB 95 disposition. CYP2B1 mRNA and CYP2B protein were not detected in brain tissues but were detected in liver. Co-exposure to nicotine and PCB 95 increased hepatic CYP2B1 mRNA but did not change CYP2B protein levels relative to vehicle control animals. However, hepatic CYP2B protein in animals co-exposed to PCB 95 and nicotine were reduced compared to animals that received only nicotine. Quantification of CYP2B3, CYP3A2 and CYP1A2 mRNA identified significant effects of nicotine and PCB 95 co-exposure on hepatic CYP3A2 and hippocampal CYP1A2 transcripts. Our findings suggest that nicotine co-exposure does not significantly influence PCB 95 disposition in the rat. However, these studies suggest a novel influence of PCB 95 and nicotine co-exposure on hepatic cytochrome P450 (P450) expression that may warrant further attention due to the increasing use of e-cigarettes and related products.

Microsomal Metabolism of Prochiral Polychlorinated Biphenyls Results in the Enantioselective Formation of Chiral Metabolites

“… 29 , 39 , 45 − 48 Extracts from microsomal incubations were analyzed using an established GC−μECD method. 24 , 28 , 49 This method is more sensitive compared to the GC–MS analysis described above. Major metabolites were identified based on their RRTs and quantified relative to the internal standard (PCB 204).…”

Effects of quercetin on Aroclor 1254-induced expression of CYP450 and cytokines in pregnant rats

“…OH-PCB). Earlier studies showed hepatic expression levels of CYP1 genes positively correlated with the concentration of each OH-PCB congener in the tissues (Nomiyama et al 2014;Stamou et al 2015). There metabolites then can impart their own distinct toxicities, including inducing causing peroxidative damage (Dreiem et al 2009), neurotoxicity (Lesmana et al 2014), and increases in fetal malformations (Juchau et al 1985).…”

“…In addition, PCBs are slowly biotransformed in the liver, leading to a delayed clearance from the body. In general, the first step in PCB metabolism is a cytochrome P 450 -dependent mono-oxygenation that results in the formation of OH-PCB; these transformations are modulated in particular by CYP1A and CYP2B isoforms (Nomiyama et al 2014;Stamou et al 2015). These hydroxylated metabolites may interact directly with estrogen receptors, as agonists or antagonists (James et al 2008), and impact on reproductive functions in humans and animals (Connor et al 1997;Fielden et al 1997;Hisada et al 2014).…”

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

“…PCBs are able to increase cell oxidative stress, including lipid peroxidation (Gadalla and Andreotti 2015 ). Also, induction of the cytochrome P450 2B family enzymes has been suggested (Stamou et al 2015 ). Moreover, a possible association between leukocyte telomere length and PCBs blood levels in the civilian US adult population has been recently revealed in research on different types of tumors using data from the National Health and Nutrition Examination Survey (Easley et al 2016 ; Zhang et al 2016 ).…”