4‐Nitrophenol exposure alters the AhR signaling pathway and related gene expression in the rat liver

Abstract

4-Nitrophenol (PNP) is well known as an environmental endocrine disruptor. The aim of this study was to clarify the mechanism of PNP-induced liver damage and determine the regulatory involvement of the aryl hydrocarbon receptor (AhR) signaling pathway and associated gene expression. Immature male Wistar-Imamichi rats (28 days old) were randomly divided into control and PNP groups, which consisted of 1- and 3-day exposure (1 DE and 3 DE, respectively) and 3-day exposure followed by 3-day recovery (3 DE + 3 DR), groups. Each group was administered the vehicle or PNP (200 mg kg body weight). The body and liver weight were significantly decreased in the 3 DE group. The mRNA expression levels of estrogen receptor-α (ERα), glutathione S-transferase (GST) and AhR exhibited a significant increase in the 1 DE group whereas, in contrast, that of cytochrome P450 (CYP) 1A1 decreased significantly in the 3 DE +3 DR group. AhR and CYP1A1 proteins were detected in the cytoplasm of hepatocytes of the 1 DE and 3 DE +3 DR groups whereas the ERα protein was found in the hepatocyte nuclei of the 1 DE and 3 DE groups. The present study demonstrates that PNP activated the AhR signaling pathway and regulated related CYP1A1 and GST gene expression in the liver. Copyright © 2016 John Wiley & Sons, Ltd.

Exposure assessment of 170 pesticide ingredients and derivative metabolites in people from the Central Andes of Peru

“…Likewise, PNP is an endocrine disruptor that has oncogenic potential 39 . PNP has been reported to exert hepatotoxic effects in rodents by increasing liver transcription levels of genes encoding the estrogen receptor-α, glutathione S-transferase, and www.nature.com/scientificreports/ aryl hydrocarbon receptor signaling pathway 40 . An intriguing finding is that similar alterations in gene expression have been described in a molecular subtype of liver cancer developed by Peruvian patients originating from the Central Andes 20,41 , which might suggest a role for PNP in promoting the disease in the region.…”

Extending non-targeted exposure discovery of environmental chemical exposures during pregnancy and their association with pregnancy complications—a cross-sectional study

“…In addition, these chemicals have short half-lives and are quickly metabolized and excreted in urine contributing to their low detection frequency in serum samples. 19,36,37 These are high production volume chemicals that may interact with endocrine and metabolic pathways; however, their relationship with adverse reproductive or pregnancy outcomes has not been previously assessed, warranting further study. Despite their low detection frequency and that they were measured in serum rather than in urine our study demonstrates that novel exposures to these environmental chemicals can still be identified through non-targeted methods and confirmed through targeted approaches.…”

“…Nine environmental chemicals were measured in maternal and cord samples using targeted approaches described below. Linear and branched isomers of perfluorooctane sulfonate (PFOS); perfluorohexane sulfonate (PFHxS); monoethylhexyl phthalate (MEHP), a metabolite of diethylhexyl phthalate, a common plasticizer 18 ; 4-nitrophenol, a known endocrine disruptor used in pesticides, dyes, and pharmaceuticals 19 ; tetraethylene glycol, a plasticizer and solvent used in metal lubricants, printing inks, and cosmetics; 20 tridecanedioic acid and octadecanedioic acid which are endogenous fatty acids that also have exogenous sources primarily from plastics synthesis; 21–23 and deoxycholic acid, a bile acid and endogenous biomarker associated with GDM (Supplemental Table 1) . 24…”

Extending Nontargeted Discovery of Environmental Chemical Exposures during Pregnancy and Their Association with Pregnancy Complications—A Cross-Sectional Study

“…Nine environmental chemicals were measured in maternal and cord serum samples using semiquantitation approaches, as described below. Linear and branched isomers of perfluorooctane sulfonate (PFOS); perfluorohexane sulfonate (PFHxS); monoethylhexyl phthalate (MEHP), a metabolite of diethylhexyl phthalate, a common plasticizer; 20 4-nitrophenol, a known endocrine disruptor used in pesticides, dyes, and pharmaceuticals; 21 tetraethylene glycol, a plasticizer and solvent used in metal lubricants, printing inks, and cosmetics; 22 tridecanedioic acid and octadecanedioic acid, abnormal fatty acids that have exogenous sources primarily from plastics synthesis; 23 – 25 and deoxycholic acid, a bile acid that is associated with GDM ( Table 1 ). 30 …”