Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring

• Published in: Toxicology letters Vol. 229; no. 1; pp. 41 - 51
• Main Authors: Esteban, Javier, Elabbas, Lubna E., Borg, Daniel, Herlin, Maria, Åkesson, Agneta, Barber, Xavier, Hamscher, Gerd, Nau, Heinz, Bowers, Wayne J., Nakai, Jamie S., Viluksela, Matti, Håkansson, Helen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 17.08.2014
• Subjects: Algorithms; Alterations; Animals; Aroclor 1254; Body Weight - drug effects; Chlorodiphenyl (54% Chlorine) - toxicity; Cytochrome P-450 Enzyme System - metabolism; Dams; Endpoint Determination; Environmental Pollutants - toxicity; Enzymes; Exposure; Female; Homeostasis - drug effects; Hormones; Kidney - metabolism; Lactation - physiology; Liver; Liver - drug effects; Liver - metabolism; Male; Medicin och hälsovetenskap; Mixed Function Oxygenases - metabolism; Organ Size - drug effects; Partial least square regression; Perinatal exposure; Polychlorinated biphenyls; Polychlorinated biphenyls (PCBs); Polychlorinated Dibenzodioxins - toxicity; Pregnancy; Rats; Rats, Sprague-Dawley; Retinoids; Retinoids - blood; Retinoids - metabolism; Serums; Thyroid Hormones - metabolism; Toxic equivalency; Vitamin A - metabolism; Aroclor 1254; Perinatal exposure; Retinoids; Toxic equivalency; Polychlorinated biphenyls (PCBs); Partial least square regression
• ISSN: 0378-4274; 1879-3169; 1879-3169
• DOI: 10.1016/j.toxlet.2014.04.021

•Gestational and lactational exposure to A1254 altered retinoid levels in liver, kidney and serum in rat dams and offspring.•Hepatic retinoids were associated with hepatic EROD, PROD and BROD, serum T3 and T4 levels as well as body and liver weights.•Both sexes showed similar retinoid alterations, which were the only observations still apparent at postnatal day 350.•Dioxin-like (DL) congeners were considered responsible for most of the observed effects according to the A1254 DL activity.•The results lend further support to the proposal by OECD to measure retinoids for identification of endocrine alterations. Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.