Transcriptome analyses demonstrate that Peroxisome Proliferator-Activated Receptor α (PPARα) activity of an ultraviolet absorber, 2-(2’-hydroxy-3’,5’-di-tert-butylphenyl)benzotriazole, as possible mechanism of their toxicity and the gender differences

Hirata-Koizumi, Mutsuko; Ise, Ryota; Kato, Harubumi; Matsuyama, Takashi; Nishimaki-Mogami, Tomoko; Takahashi, Mika; Ono, Atsushi; Ema, Makoto; Hirose, Akihiko

doi:10.2131/jts.41.693

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…BPA, another plastic additive, may bind to estrogen receptors and interfere with estrogen signaling to elicit obesogenic effects (201). Similarly, UV filters such as benzotriazoles (202), flame retardants such as HBCD (203) and BPA (204) have been shown to affect adipogenesis in laboratory animals. Obesogens are believed to act through binding to PPAR isoforms that results in a cascade of activities affecting cellular functions.…”

Section: Toxic Mechanisms Of Microplastics In Relation To Obesitymentioning

confidence: 99%

A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens

2021

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The ubiquitous exposure of humans to microplastics (MPs) through inhalation of particles in air and ingestion in dust, water, and diet is well established. Humans are estimated to ingest tens of thousands to millions of MP particles annually, or on the order of several milligrams daily. Available information suggests that inhalation of indoor air and ingestion of drinking water bottled in plastic are the major sources of MP exposure. Little is known on the occurrence of MPs in human diet. Evidence is accumulating that feeding bottles and medical devices can contribute to MP exposure in newborns and infants. Biomonitoring studies of human stool, fetus, and placenta provide direct evidence of MP exposure in infants and children. MPs <20 µm were reported to cross biological membranes. Although plastics were once perceived as inert materials, MP exposure in laboratory animals is linked to various forms of inflammation, immunological response, endocrine disruption, alteration of lipid and energy metabolism, and other disorders. Whereas exposure to MPs itself is a concern, MPs can also be sources of exposure to plastic additives and other toxicants. Exposure of human cell lines to MP additives such as phthalates, bisphenols, and organotins causes adverse effects through the activation of nuclear receptors, peroxisome proliferator-activated receptors (PPARs) α, β, and γ, and retinoid X receptor (RXR), leading to oxidative stress, cytotoxicity, immunotoxicity, thyroid hormone disruption, and altered adipogenesis and energy production. The size, shape, chemical composition, surface charge, and hydrophobicity of MPs influence their toxicity. Maternal transfer of MPs to the developing fetus has been demonstrated in exposed laboratory animals and through the analysis of human placenta. In laboratory animal studies, maternal exposure to MPs altered energy and lipid metabolism in offspring and subsequent generations. Moreover, concomitant with the global increase in plastics production, the prevalence of overweight and obesity in human populations has increased over the past five decades, and there is evidence to support the hypothesis that MPs and their additives are potential obesogens. Even though MP exposures are ubiquitous and toxic effects from such exposures are a concern, systematic studies on this topic remain urgently needed.

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Section: Toxic Mechanisms Of Microplastics In Relation To Obesitymentioning

confidence: 99%

A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens

2021

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“…Hirata- Koizumi et al (2007Koizumi et al ( , 2008Koizumi et al ( , 2016 reported that UV-320 showed gender-dependent hepatotoxicity in rats, inducing CYP4A-specific lauric acid 12-hydroxylase activity. As a possible mechanism, they suggested hepatotoxicity through the PPARα signaling pathway, based on gender-specific enhancement of the expression of PPARα mRNA in rat liver after the administration of UV-320.…”

Section: Discussionmentioning

confidence: 99%

Effects of benzotriazole ultraviolet stabilizers on rat PXR, CAR and PPARα transcriptional activities

Watanabe

Hattori

Fujino

et al. 2019

Fundam. Toxicol. Sci.

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Benzotriazole ultraviolet stabilizers (BUVSs) are widely used as ultraviolet filters in various consumer and industrial products. For this purpose, we examined the effects of 10 BUVSs and benzotriazole itself on transcriptional activation mediated by nuclear receptors: pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor alpha (PPARα). UV-090 and UV-9 showed rat PXR-agonistic activity in the concentration range of 1-30 μM in reporter gene assay using simian kidney COS-1 cells. UV-090 showed the highest activity (REC 20 value: 3.85 × 10-6 M). UV-090 was also positive in rat CAR activation assay, while UV-P showed inverse agonistic activity towards CAR. In the presence of the CAR agonist artemisinin (10 μM), UV-P also showed dose-dependent CAR-antagonistic activity in the concentration range of 10-30 μM. UV-090 and UV-9 activated rat PPARα. Overall, these results suggest that UV-090, UV-9 and UV-P modulate PXR, CAR and/or PPARα activation.

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“…It is reported that activation of AhR could affect proinflammatory and anti‐inflammatory responses (eg, promotion of T‐cell differentiation, induction of immune‐responsive cytokines) and induce immune responses . Additionally, UV‐320 has been shown to induce sex‐dependent hepatotoxicity through the peroxisome proliferator‐activated receptor α (PPARα) pathway . PPARs, members of the nuclear receptor family, can influence cell proliferation as well as the immune and inflammatory response in different tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals benzotriazole ultraviolet stabilizers regulate networks related to inflammation in juvenile zebrafish (Danio rerio) brain

Zha

et al. 2018

Environmental Toxicology

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Benzotriazole ultraviolet stabilizers (BUVSs) are widely applied ultraviolet absorbing compounds in industrial materials and personal care products. Due to their ubiquitous use and reports of bio-accumulation in aquatic organisms, these compounds are significant environmental pollutants; however, data are limited for BUVSs toxicity. In this study, juvenile zebrafish (Danio rerio) were exposed to 4 commonly used BUVSs (UV-234, UV-326, UV-329, and UV-P) at one dose of 10 or 100 μg/L for 28 days. To characterize the underlying mechanisms of different BUVSs-induced toxicities, we performed global transcriptome sequencing (RNA-Seq) in the brain (100 μg/L). There were 390, 575, 483, and 470 differentially expressed genes (DEGs) detected following UV-234, UV-326, UV-329, and UV-P exposure at 100 μg/L, respectively. Only 59 genes were identified as DEGs following exposure to each of the BUVSs, suggesting that these chemicals can induce unique responses in fish. Noteworthy was that there were 81 common gene networks (~10%) identified following exposure to BUVSs, many of which were related to inflammation and immune function. Uniquely regulated pathways affected by different BUVSs included those related to mitochondrial respiration, interleukin 1/brain-damaging signaling, dopaminergic signaling, and adrenergic receptor cascades. Furthermore, quantitative PCR (qPCR) results revealed that mgst1 levels were increased in fish from the 100 μg/L UV-329 treatment, while the expression of pck2 was significantly down-regulated in fish from both the 10 and 100 μg/L UV-P treatment.Transcriptomic data suggest that BUVSs can alter mitochondrial bioenergetics, alter expression of a broad range of genes in the oxidative stress response, and can induce pathways related to the immune system in zebrafish brain. K E Y W O R D Sbenzotriazole ultraviolet stabilizers, immune-related pathways, juvenile zebrafish, RNA-Seq

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Transcriptome analyses demonstrate that Peroxisome Proliferator-Activated Receptor α (PPARα) activity of an ultraviolet absorber, 2-(2’-hydroxy-3’,5’-di-tert-butylphenyl)benzotriazole, as possible mechanism of their toxicity and the gender differences

Cited by 8 publications

References 28 publications

A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens

A Review of Human Exposure to Microplastics and Insights Into Microplastics as Obesogens

Effects of benzotriazole ultraviolet stabilizers on rat PXR, CAR and PPARα transcriptional activities

Transcriptome analysis reveals benzotriazole ultraviolet stabilizers regulate networks related to inflammation in juvenile zebrafish (Danio rerio) brain

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