Dose‐dependent stimulation of hepatic retinoic acid hydroxylation/oxidation and glucuronidation in brook trout, Salvelinus fontinalis, after exposure to 3,3′,4,4′‐tetrachlorobiphenyl

Abstract

Abstract-Extremely low stores of vitamin A have been reported in fish and birds inhabiting regions contaminated by coplanar polychlorinated biphenyls (PCBs) and other organochlorines, suggesting many possible effects on retinoid biochemical pathways. Metabolic imbalances associated with biologically active retinoids (e.g., retinoic acid) could be associated with teratogenesis, edema, growth inhibition, reproductive impairment, immunosuppression, and susceptibility to cancer. Sexually mature brook trout were injected intraperitoneally with the coplanar PCB 3,3Ј,4,4Ј-tetrachlorobiphenyl (TCBP) and again 4 weeks later. At 8 weeks, retinoic acid metabolism was measured in liver microsomes. To our knowledge, retinoic acid conjugation by UDP-glucuronyltransferase is described here for the first time in fish. A substantial rate of glucuronidation was detected in the microsomes from control brook trout, which tended to increase over the dose range of TCBP. Glucuronidation was significantly greater in fish receiving the 10 g/ g body weight dose level. Metabolism through the cytochrome P450 system was also dose-dependent, resulting in significantly greater production of 4-hydroxyretinoic acid at the 10 g/g dose level. In contrast, subsequent oxidation to 4-oxo-retinoic acid was greatest at the 1 g/g dose level and did not increase further at higher doses. Liver stores of dehydroretinyl palmitate/oleate were significantly decreased at the 5 and 10 g/g dose levels.

Effects of polychlorobiphenyls, polybromodiphenylethers, organochlorine pesticides and their metabolites on vitamin A status in lactating grey seals

“…Increases in the circulating vitamin A after exposure to PCBs have already been reported in rats and were linked to a reduction of hepatic retinoid stores (Bank et al, 1989;Zile , 1992), suggesting an enhanced mobilisation of hepatic vitamin A in PCB exposed animals. A reduction of hepatic retinoid stores following PCB exposure has also been observed in fish (Boyer et al, 2000), birds (Bishop et al, 1999;Murk et al, 1994) and aquatic mammals Nyman et al, 2003). Although several in vivo and in vitro studies showed that the activity of different liver enzymes involved in the retinoid metabolism were modified following PCB exposure (Fig.…”

“…In the liver, contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), PCBs and pesticides were able to modulate the regulation of some cytochrome P450 (CYP) enzymes that are also involved in the metabolism and the catabolism of retinoic acid (Fig. 1, points 1 and 2) (Boyer et al, 2000, Leiva-Presa et al, 2006Nová k et al, 2008). The activity of enzymes that esterify retinol and hydrolyse retinyl esters such as retinyl ester hydrolase (REH), acyl-CoA:retinol acyltransferase (ARAT) and lecithin:retinol acyltransferase (LRAT) were also shown to be modulated by PCBs and TCDD in fish and laboratory animals ( Fig.…”

Oxidation of retinoic acids in hepatic microsomes of wild bullfrogs Lithobates catesbeianus environmentally-exposed to a gradient of agricultural contamination

“…Hepatic oxidative catabolism of RA has been reported in non-mammalian vertebrates classes: fish (Gilbert et al 1995;Boyer et al 2000) and birds (Swindell et al 1999). Whereas the genes associated with RA metabolism clearly evolved long before the appearance of vertebrates (Albalat 2009) and amphibian models are widely used to study RA-related mechanisms in amphibian embryo development (e.g.…”

“…Procedures to assay the RA conversion to 4-oxo-RA were conducted under yellow incandescent light to prevent spontaneous isomerization of retinoids and according to the method of Boyer et al (2000), with slight modifications. A stock solution of 3.0 mM atRA or 13cisRA in methanol 100 % was kept at -20°C and checked regularly for purity by comparing spectrometer and HPLC chromatograms.…”