Tetrabromobisphenol A activates the hepatic interferon pathway in rats

Dunnick, June K.; Morgan, Daniel L.; Elmore, Susan A.; Gerrish, Kevin; Pandiri, Arun R.; Ton, Thai-Vu; Shockley, Keith R.; Merrick, B. Alex

doi:10.1016/j.toxlet.2016.11.019

Cited by 23 publications

(14 citation statements)

References 62 publications

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“…Dunnick et al (2016) further found that 13 weeks of repeat TBBPA exposure (1000 mg/kg) in female Wistar Han rats activated the interferon pathway in the liver, adding evidence to the hypothesis that long-term exposure to TBBPA could result in immunomodulatory changes that promote cancer.…”

Section: Discussionmentioning

confidence: 83%

Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

et al. 2017

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Tetrabromobisphenol A (TBBPA) is a brominated flame retardant used globally at high volumes, primarily in the epoxy resin of circuit boards. It has been detected in the environment and in humans. The National Toxicology Program found that chronic oral TBBPA treatment of 250 mg/kg and higher caused an increased incidence of uterine lesions in female Wistar Han rats. The present laboratory has previously reported changes in gene expression associated with estrogen homeostasis in liver and uterine tissue of adult female Wistar Han rats after five days of gavage with 250 mg/kg of TBBPA. Microarray analysis of tissue from these same TBBPA-treated rats was performed to detect additional pathways perturbed by TBBPA. Microarray analysis of uterine tissue detected downregulation of genes in pathways of the immune response following TBBPA treatment. These results, along with validation of associated gene expression changes using droplet digital PCR, are reported here. Our findings suggest mechanisms that may be related to estrogen-mediated immunosuppression.

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Section: Discussionmentioning

confidence: 83%

Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

et al. 2017

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“…[ 33 , 34 ]), and studies have shown that dietary supplementation of bile acids can affect the activity of intestinal and lipoprotein lipases leading to improvement of broiler chicken growth [ 35 , 36 ]. PARP12 gene, on the other hand, is a polymerase family member and found to be involved in regulating fatty acid metabolism [ 37 ] as well as body weight gain and insulin resistance in rats [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study reveals candidate genes relevant to body weight in female turkeys (Meleagris gallopavo)

et al. 2022

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The underlying genetic mechanisms affecting turkey growth traits have not been widely investigated. Genome-wide association studies (GWAS) is a powerful approach to identify candidate regions associated with complex phenotypes and diseases in livestock. In the present study, we performed GWAS to identify regions associated with 18-week body weight in a turkey population. The data included body weight observations for 24,989 female turkeys genotyped based on a 65K SNP panel. The analysis was carried out using a univariate mixed linear model with hatch-week-year and the 2 top principal components fitted as fixed effects and the accumulated polygenic effect of all markers captured by the genomic relationship matrix as random. Thirty-three significant markers were observed on 1, 2, 3, 4, 7 and 12 chromosomes, while 26 showed strong linkage disequilibrium extending up to 410 kb. These significant markers were mapped to 37 genes, of which 13 were novel. Interestingly, many of the investigated genes are known to be involved in growth and body weight. For instance, genes AKR1D1, PARP12, BOC, NCOA1, ADCY3 and CHCHD7 regulate growth, body weight, metabolism, digestion, bile acid biosynthetic and development of muscle cells. In summary, the results of our study revealed novel candidate genomic regions and candidate genes that could be managed within a turkey breeding program and adapted in fine mapping of quantitative trait loci to enhance genetic improvement in this species.

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“…TCBPA treatment of mice significantly induced secretion of various pro-inflammatory cytokines (IL-2, IL-12, TNF-α, and IFN-γ) and immunosuppressive cytokines (IL-4, IL-5, IL-10, GM-CSF) in serum, suggesting immunosuppressive property of TCBPA [ 186 ]. Moreover, the transcriptomic analysis revealed that TBBPA induced changes in expression levels of transcripts associated with hepatic IFN pathway regulation and genes regulating fatty acid metabolism in rats [ 187 ]. TBBPA has also been shown to induce adipogenesis (lipid accumulation) in mouse-derived preadipocytes cell culture [ 188 ].…”

Section: Biological Actions Of Frs: Role In Inflammatory and Cytokine Signalingmentioning

confidence: 99%

Flame Retardants-Mediated Interferon Signaling in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Negi

Khan

Dirven

et al. 2021

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is a growing concern worldwide, affecting 25% of the global population. NAFLD is a multifactorial disease with a broad spectrum of pathology includes steatosis, which gradually progresses to a more severe condition such as nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and eventually leads to hepatic cancer. Several risk factors, including exposure to environmental toxicants, are involved in the development and progression of NAFLD. Environmental factors may promote the development and progression of NAFLD by various biological alterations, including mitochondrial dysfunction, reactive oxygen species production, nuclear receptors dysregulation, and interference in inflammatory and immune-mediated signaling. Moreover, environmental contaminants can influence immune responses by impairing the immune system’s components and, ultimately, disease susceptibility. Flame retardants (FRs) are anthropogenic chemicals or mixtures that are being used to inhibit or delay the spread of fire. FRs have been employed in several household and outdoor products; therefore, human exposure is unavoidable. In this review, we summarized the potential mechanisms of FRs-associated immune and inflammatory signaling and their possible contribution to the development and progression of NAFLD, with an emphasis on FRs-mediated interferon signaling. Knowledge gaps are identified, and emerging pharmacotherapeutic molecules targeting the immune and inflammatory signaling for NAFLD are also discussed.

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Tetrabromobisphenol A activates the hepatic interferon pathway in rats

Cited by 23 publications

References 62 publications

Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

Genome-wide association study reveals candidate genes relevant to body weight in female turkeys (Meleagris gallopavo)

Flame Retardants-Mediated Interferon Signaling in the Pathogenesis of Nonalcoholic Fatty Liver Disease

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