Comparative hepatic activity of xenobiotic‐metabolizing enzymes and concentrations of organohalogens and their hydroxylated analogues in captive greenland sledge dogs (Canis familiaris)

Abstract

A captive study was performed with Greenland sledge dogs (Canis familiaris) fed a naturally organohalogen-contaminated diet (Greenland minke whale [Balaenoptera acutorostrata] blubber; exposed group) or a control diet (pork fat; control group). The catalytic activity of major xenobiotic-metabolizing phase I and II hepatic microsomal enzymes was assessed. Relative to control dogs, ethoxyresorufin-O-deethylase (EROD) activity in exposed dogs was twofold higher (p = 0.001). Testosterone hydroxylation yielded 6beta- and 16beta-hydroxy (OH) testosterone and androstenedione, with higher rates of production (23-27%; p < or = 0.03) in the exposed individuals. In the exposed dogs, epoxide hydrolase (EH) activity was 31% higher (p = 0.02) relative to the control dogs, whereas uridine diphosphoglucuronosyl transferase (UDPGT) activity was not different (p = 0.62). When the exposed and control dogs were combined, the summed (sigma) plasma concentrations of OH-polychlorinated biphenyl (PCB) congeners were predicted by plasma sigmaPCB concentrations and EROD activity (p < or = 0.04), whereas testosterone hydroxylase, EH, and UDPGT activities were not significant predictors of these concentrations. Consistent results were found for individual OH-PCB congeners and their theoretical precursor PCBs (e.g., 4-OH-CB-187 and CB-183, and 4-OH-CB-146 and CB-146) and for EROD activity. No association was found between sigmaOH-polybrominated diphenyl ether (PBDE) and sigmaPBDE plasma concentrations, or between potential precursor-metabolite pairs, and the enzyme activities. The present results suggest that liver microsomal EROD activity and plasma PCB concentrations have a greater (e.g., relative to EH activity) predictive power for the occurrence of plasma OH-PCB residues in sledge dogs. These results also suggest that plasma OH-PBDEs likely are not products of cytochrome P450-mediated transformation but, rather, are accumulated via the diet.

Steroid hormones in blood plasma from Greenland sledge dogs (Canis familiaris) dietary exposed to organohalogen polluted minke whale (Balaenoptera acuterostrata) blubber

“…Organohalogen contaminant (organochlorines and brominated flame retardants) analysis in blood plasma and fat samples were conducted in the Letcher Research Labs at the National Wildlife Research Centre, Carleton University, Ottawa, Canada, according to methods described in detail elsewhere (Verreault et al 2008(Verreault et al , 2009a(Verreault et al , 2009bDietz et al 2004Dietz et al , 2007Dietz et al , 2013aDietz et al , 2013bGauthier et al 2009;Gebbink et al 2008;Muir et al 2006). Briefly, the S 59 PCB was based on the sum of the following 59 congeners: CB16/32,17,18,22,31/28,33/20,42,44,47/48,52,56/60,64/41,66,70/76,74,85,87,92,95,97,99,101/90,105,110,114,118,128,130,137,138,141,146,149,151,153,156,157,158,170/190,171,172,174,176,177,…”

“…The impact of OHC on steroid production and distribution in Arctic top predators is essentially unknown, although a few hormones, mainly TS, b-E2, progesterone (PRO), and cortisol, were investigated in polar bears, arctic foxes (Alopex lagopus), and sledge dogs (Canis familiaris) (Tryland et al 2002;Haave et al 2003;Oskam et al 2004;Sonne et al 2008a;Verreault et al 2009b;Letcher et al 2010;Sonne 2010;Villanger et al 2011;Bechshøft et al 2012aBechshøft et al , 2012bGustavson, Ciesielski, Bytingsvik, Styrishave, Hansen, Aars et al Submitted for publication;Gustavson, Ciesielski, Bytingsvik, Styrishave, Hansen, Lie et al Submitted for publication). Overall, studies indicate a decrease in circulating blood steroid titers during OHC exposure although OHCs responsible for this apparent fall and the mechanisms by which they produce it are unknown.…”

Seasonal emaciation causes tissue redistribution and an increased potential for toxicity of lipophilic pollutants in farmed arctic fox (Vulpes lagopus)

“…A moderate (2-fold) CYP1A induction has also been seen in sledge dogs experimentally contaminated with minke whale blubber [24]. Unfortunately, the liver SPCB concentrations in the sledge dog were not given, but the SPCB concentrations in blood (11.9 ng/g wet wt) and adipose tissue (1,500-4,500 ng/g wet wt) in the sledge dogs [24,41] were quite similar to those seen in the foxes used in the present study (10.1-85.7 ng/g and 1000-4000 ng/g wet wt, respectively). These concentrations of SPCB may represent a threshold for CYP1A induction in these species when they are contaminated with an environmentally realistic OC cocktail in the Arctic.…”

“…Taking into account the high absorption efficiencies of PCBs found in the present study, the low tissue accumulation of PCBs suggests an efficient biotransformation and elimination of PCBs in the Arctic fox. As far as we know, no data have been published on PCB metabolites in the Arctic fox; however, the plasma concentrations of hydroxy-PCB metabolites have been analyzed and were considered high in red foxes (Vulpes vulpes; a close relative to Arctic fox) from Norway [23] and contaminant exposed sledge dogs (Canis familiaris) from Greenland [24]. The concentrations of SOC in adipose tissue and liver obtained in the present experimental study were within the range of those seen in wild Arctic fox from Alaska, Canada, and Svalbard [4,25].…”

Physiologically-based pharmacokinetic modelling of distribution, bioaccumulation and excretion of POPs in Greenland sledge dogs (Canis familiaris)

“…The Aasiaat study focused on relevant dietary POP exposures for Arctic top predators and the subsequent health effects on multiple organ-systems. A detailed description and discussion of concentrations of pollutants, lipids and nutrients in the diet has been published previously by Sonne, (2010), Kirkegaard et al, (2011), Sonne et al, (2006b, 2007b, 2007c, 2008a, 2008b, 2008c, 2010, 2014b, 2014c and Verreault et al, (2009aVerreault et al, ( , 2009b.…”