Short-term Exposure to Triclosan Decreases Thyroxine In Vivo via Upregulation of Hepatic Catabolism in Young Long-Evans Rats

Abstract

Triclosan (5-chloro-2-(2,4-dichlorophenoxy)-phenol) is a chlorinated phenolic antibacterial compound found in consumer products. In vitro human pregnane X receptor activation, hepatic phase I enzyme induction, and decreased in vivo total thyroxine (T4) suggest adverse effects on thyroid hormone homeostasis. Current research tested the hypothesis that triclosan decreases circulating T4 via upregulation of hepatic catabolism and transport. Weanling female Long-Evans rats received triclosan (0-1000 mg/kg/day) by gavage for 4 days. Whole blood and liver were collected 24 h later. Total serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay. Hepatic microsomal assays measured ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase (PROD), and uridine diphosphate glucuronyltransferase enzyme activities. The messenger RNA (mRNA) expression of cytochrome P450s 1a1, 2b1/2, and 3a1/23; UGTs 1a1, 1a6, and 2b5; sulfotransferases 1c1 and 1b1; and hepatic transporters Oatp1a1, Oatp1a4, Mrp2, and Mdr1b was measured by quantitative reverse transcriptase PCR. Total T4 decreased dose responsively, down to 43% of control at 1000 mg/kg/day. Total T3 was decreased to 89 and 75% of control at 300 and 1000 mg/kg/day. TSH did not change. Triclosan dose dependently increased PROD activity up to 900% of control at 1000 mg/kg/day. T4 glucuronidation increased nearly twofold at 1000 mg/kg/day. Cyp2b1/2 and Cyp3a1/23 mRNA expression levels were induced twofold and fourfold at 300 mg/kg/day. Ugt1a1 and Sult1c1 mRNA expression levels increased 2.2-fold and 2.6-fold at 300 mg/kg/day. Transporter mRNA expression levels were unchanged. These data denote important key events in the mode of action for triclosan-induced hypothyroxinemia in rats and suggest that this effect may be partially due to upregulation of hepatic catabolism but not due to mRNA expression changes in the tested hepatic transporters.

Durability of the anti-erosive effect of surfaces sealants under erosive abrasive conditions

“…Recent studies have shown that triclosan is able to induce antibiotic resistances in various bacteria stems [43], to accumulate in human milk samples and in fish exposed to municipal wastewater [44], to be found in biosolids which might be spread on agricultural land (also causing adverse effects in the soil environment [45]) and to reduce serum thyroid hormone levels following oral administration [46]. Due to these findings, concerns about the use of triclosan have been raised.…”

Triclosan exposure results in alterations of thyroid hormone status and retarded early development and metamorphosis in Cyprinodon variegatus

“…Studies on other aquatic vertebrates such as frogs have shown that environmentally relevant levels of triclosan can disrupt the expression profile of thyroid hormone receptors (Veldhoen et al, 2006) and the expression of TR␣ (Fort et al, 2009). Studies on rats showed no significant effects of triclosan on thyroid histology (Zorrilla et al, 2009) or thyroid mass (Axelstad et al, 2013) but they revealed a consistent dose-dependent decline in serum T4 whereas the decrease in serum T3 was less pronounced (Axelstad et al, 2013;Crofton et al, 2007;Paul et al, 2009;Stoker et al, 2010;Zorrilla et al, 2009). These studies suggest that the brain-pituitary-thyroid axis that regulates T4 biosynthesis and secretion is not affected by triclosan exposure.…”

“…The first study to indicate that triclosan is capable of inhibiting sulfation of thyroid hormones was performed by Schuur et al, 1998, who studied the in vitro inhibition of diiodothyronine (T2) sulfotransferase activity using rat liver cytosol (Schuur et al, 1998). Studies on rats gavaged with triclosan revealed an increased T4-glucuronidation activity (Paul et al, 2009;Zorrilla et al, 2009). The contribution of other mechanisms of triclosaninduced thyroid hormone deficiency, such as impaired deiodinase activity or competitive binding to thyroid hormone serum proteins, have been even less explored (Butt et al, 2011).…”

P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the Hypothyroidism of Triclosan-Treated Rats

“…A mode of action involved activations of pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which induced activities of hepatic phases I and II enzymes and ultimately increased clearance of THs from the body [6]. Moreover, the study also reported that triclosan could accelerate the biliary excretion of THs through inducing TH sulfation [6].…”