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Dibutyl Phthalate (DBP)

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The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate

Authors: Liu, ZH; Li, EH; Xu, DL; Sun, WL; Hong, Y; Zhao, W; Xia, SJ; Jiang, JT (2016) Environmental Toxicology 31:261-268. HERO ID: 2510780

[Less] This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal . . . [More] This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Dibutyl Phthalate Exposure Disrupts Evolutionarily Conserved Insulin and Glucagon-Like Signaling in Drosophila Males

Authors: Williams, MJ; Wiemerslage, L; Gohel, P; Kheder, S; Kothegala, LV; Schioth, HB (2016) Endocrinology 157:2309-2321. HERO ID: 3350270

[Less] Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care . . . [More] Phthalate diesters are commonly used as industrial plasticisers, as well as in cosmetics and skin care products, as a result people are constantly exposed to these xenobiotics. Recent epidemiological studies have found a correlation between circulating phthalate levels and type 2 diabetes, whereas animal studies indicate that phthalates are capable of disrupting endocrine signaling. Nonetheless, how phthalates interfere with metabolic function is still unclear. Here, we show that feeding Drosophila males the xenobiotic dibutyl phthalate (DBP) affects conserved insulin- and glucagon-like signaling. We report that raising flies on food containing DBP leads to starvation resistance, increased lipid storage, hyperglycemia, and hyperphagia. We go on to show that the starvation-resistance phenotype can be rescued by overexpression of the glucagon analogue adipokinetic hormone (Akh). Furthermore, although acute DBP exposure in adult flies is able to affect insulin levels, only chronic feeding influences Akh expression. We establish that raising flies on DBP-containing food or feeding adults DBP food affects the expression of homologous genes involved in xenobiotic and lipid metabolism (AHR [Drosophila ss], NR1I2 [Hr96], ABCB1 [MDR50], ABCC3 [MRP], and CYP3A4 [Cyp9f2]). Finally, we determined that the expression of these genes is also influenced by Akh. Our results provide comprehensive evidence that DBP can disrupt metabolism in Drosophila males, by regulating genes involved in glucose, lipid, and xenobiotic metabolism.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Changes of c-Myc and DNMT1 mRNA and protein levels in the rat livers induced by dibutyl phthalate treatment

Authors: Urbanek-Olejnik, K; Liszewska, M; Winczura, A; Kostka, G (2016) Toxicology and Industrial Health 32:801-808. HERO ID: 2219793

[Less] We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc . . . [More] We investigated the relationship between dibutyl phthalate (DBP)-induced hypomethylation of the c-Myc promoter region (as evident in our early study) and the expression of c-Myc and DNMT1 genes (at messenger RNA (mRNA) and protein level) in the rat liver. Male Wistar rats received DBP in 1, 3, or 14 daily doses of 1800 mg kg(-1) body weight. Levels of DNMT1, c-Myc mRNA, and proteins were detected using real-time polymerase chain reaction and Western blot analysis, respectively. Our findings indicate that DBP caused an increase in mRNA levels of c-Myc at all time points. The results showed that protein levels of c-Myc in rat liver also increased significantly by DBP treatment, which were more pronounced at last time point (after 14 doses). Furthermore, overexpression of DNMT1gene have been found after one dose of DBP, which was confirmed at the protein level by Western blot analysis. Reduced levels of DNMT1mRNA and proteins (3 and 14 doses) were coordinated with depletion DNA synthesis (reported previously). Based on our previous results and those presented here, the following conclusion could be drawn: (1) DBP exerted biological activity through epigenetic modulation of c-Myc gene expression; (2) it seems possible that DBP-induced active demethylation of c-Myc gene through mechanism(s) linked to generation of reactive oxygen species by activated c-Myc; and (3) control of DNA replication was not directly dependent on c-Myc transcriptional activity and we attribute this finding to DNMT1gene expression which was tightly coordinated with DNA synthesis.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

PGE2 regulating Cx43 to affect testosterone synthesis in rats leydig cell exposed at DBP

Authors: Zhang, J; Zhang, Yi; Zhao, JinC; Li, H (2016) HERO ID: 3350288

[Less] To observe the effect of dibutyl phthalate (DBP) on connexin 43 (Cx43) proteins in rat testicular Leydig . . . [More] To observe the effect of dibutyl phthalate (DBP) on connexin 43 (Cx43) proteins in rat testicular Leydig cells and testosterone secretion induced by Cx43, and to investigate whether Cx43 is involved in the regulation of testosterone by DBP. Purified Leydig cells of the primary culture were divided into 3 groups, 50 mu g/ml DBP treatment group, 50 mu g/ml DBP+ 10 mu mol/L PGE2 group and DMSO control group, which were processed for 24 hours, respectively. Expression of Cx43 on cell membrane was detected by immunofluorescence, and total protein level of Cx43 was evaluated by Western blot. Testosterone production was detected by testosterone kit. Compared with control group, Cx43 expression and testosterone levels were both significantly reduced after DBP processing for 24 hours (P<0.05). Compared with DBP group, the addition of Cx43 enhancer (PGE2) enabled Cx34 expression recovery, but the change of testosterone level was insignificant (P>0.05). Both testosterone and Cx43 can be regulated by DBP. However, the inhibitory effect of DBP on testosterone synthesis in Leydig cells may not be necessarily achieved through the regulation of Cx43 expression.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Quantitative proteomic analyses of mammary organoids reveals distinct signatures after exposure to environmental chemicals

Authors: Williams, KE; Lemieux, GA; Hassis, ME; Olshen, AB; Fisher, SJ; Werb, Z (2016) Proceedings of the National Academy of Sciences 113:E1343-E1351. HERO ID: 3350269

[Less] Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such . . . [More] Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastoma-associated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The effect of di-n-butyl phthalate on testis and the potential protective effects of resveratrol

Authors: Güllen Ünal, S; Take, G; Erdoğan, D; Göktas, G; Sahin, E (2016) Toxicology and Industrial Health 32:777-790. HERO ID: 2219795

[Less] This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage . . . [More] This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Characterization of the binding between phthalate esters and mouse PPAR alpha for the development of a fluorescence polarization-based competitive binding assay

Authors: Zhang, Jie; Xing, X; Sun, Y; Li, Z; Xue, P; Wang, T; Li, T (2016) Analytical Methods 8:880-885. HERO ID: 3350287

[Less] The binding of phthalate esters (PAEs) to peroxisome proliferator-activated receptor alpha (PPAR alpha) . . . [More] The binding of phthalate esters (PAEs) to peroxisome proliferator-activated receptor alpha (PPAR alpha) has been investigated by using fluorescence polarization (FP) in combination with molecular modeling techniques. The FP competitive binding assay is based on a mouse-derived recombinant PPARa ligand binding domain (LBD) and a fluorescent-labeled fatty acid (C4-BODIPY-C9). A soluble mPPAR alpha-LBD protein derivative, named mPPAR alpha-LBD*, was expressed and purified. By using C4-BODIPY-C9 as a probe, 10 common PAEs with different carbon chain lengths and functional groups were assessed for their binding affinities with mPPAR alpha-LBD*, respectively. PAEs displace the probe from the C4-BODIPY-C9-mPPAR alpha-LBD* complex, resulting in lower polarization values. FP assay showed that PAEs compete for the C4-BODIPY-C9 binding sites in a concentration-dependent manner, and the potency of the tested PAEs increases with increasing side chain length. Molecular docking suggested that the length and hydrophobicity of the side chain of PAEs have contributed a lot to the ligand-receptor binding, and there are four prominent interactions observed to stabilize the PAEs-mPPAR alpha-LBD* binding. In addition, comparison of docking scores vs. experimental binding affinities yielded a good correlation (R-2 = 0.948). The most active DEHP (K-d = 19.6 +/- 1.7 mu M) has the lowest ranking on docking scores. The fluorescence polarization-based competitive binding assay can potentially be used for high-throughput screening of PAEs, which may serve as an assistant of chromatographic techniques.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Dibutyl maleate and dibutyl fumarate enhance contact sensitization to fluorescein isothiocyanate in mice

Authors: Matsuoka, T; Kurohane, K; Suzuki, W; Ogawa, E; Kobayashi, K; Imai, Y (2016) Biological and Pharmaceutical Bulletin 39:272-277. HERO ID: 3070943

[Less] Di-n-butyl phthalate (DBP), a phthalate ester, has been shown to have an adjuvant effect on fluorescein . . . [More] Di-n-butyl phthalate (DBP), a phthalate ester, has been shown to have an adjuvant effect on fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse models. Di-n-butyl maleate (DBM), widely used as a plasticizer for industrial application, has been reported to cause dermatitis in humans. DBM is a butyl alcohol ester of di-carboxylic acid that represents a part of the DBP structure, while di-n-butyl fumarate (DBF) is a trans isomer of DBM. We examined whether DBM or DBF exhibits an adjuvant effect like DBP does. When BALB/c mice were epicutaneously sensitized with FITC in the presence of DBM or DBF, the FITC-specific CHS response was enhanced, as we have observed for DBP. As to underlying mechanisms, DBM and DBF facilitated the trafficking of FITC-presenting CD11c(+) dendritic cells (DCs) from skin to draining lymph nodes and increased the cytokine production by draining lymph nodes. In conclusion, DBM and DBF may have an effect that aggravates contact dermatitis through a skin sensitization process.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats

Authors: Motohashi, M; Wempe, MF; Mutou, T; Okayama, Y; Kansaku, N; Takahashi, H; Ikegami, M; Asari, M; Wakui, S (2016) Journal of Toxicological Sciences 41:195-206. HERO ID: 3324167

[Less] Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) . . . [More] Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the 100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

An ultra-sensitive monoclonal antibody-based enzyme-linked immunosobent assay for dibutyl phthalate in human urinary

Authors: Zhou, L; Lei, Y; Zhang, D; Ahmed, S; Chen, S (2016) Science of the Total Environment 541:570-578. HERO ID: 3045466

[Less] Dibutyl phthalate (DBP) has been extensively used as a plasticizer in many daily products, which is . . . [More] Dibutyl phthalate (DBP) has been extensively used as a plasticizer in many daily products, which is highly toxic to human, notably affecting the reproductive and developmental function. As the previous method is expensive, time-consuming, low sensitivity and just focused on the environment. Present study was aimed to establish an ultra-sensitive and simple method based on good quality monoclonal antibody, applying to evaluate excretion level of DBP in urine samples of Chinese population directly. A monoclonal antibody was generated and characterized after fusion of myeloma cells with spleen cells isolated from BALB/c mouse. The mouse was previously immunized using a specially designed amino derivative of DBP conjugated with bovine serum albumin (BSA) as immunogen. Cross-reactivity values of the monoclonal antibody against DBP, di-isobutyl phthalate (DIBP) were observed 100% and 1.25%, while for dimethyl phthalate (DMP), butyl benzyl phthalate (BBP) and didecyl phthalate (DDP) the values were <0.06%. The standard curve was constructed at 0-50ngmL(-1) and good linearity (R(2)=0.994) was achieved. The observed IC50 (7.34ngmL(-1)) and LOD (0.06ngmL(-1)) values was improved 1000-fold to polyclonal antibody and 5-fold to other monoclonal antibodies. A total 1246 urine samples were analyzed and the detection frequency of DBP was observed 72.87% by ic-ELISA. The 95th percentile and mean concentration of DBP were 12.07 and 3.00ngmL(-1). Acceptable recovery rates of DBP were 97.8-114.3% and coefficients variation 5.93-11.09%. The concentrations of DBP in females were found significantly higher (p<0.05) than males. Similarly, the DBP in middle aged and low educated individuals was found higher (p<0.001) than the others. Considering the adverse health effects, DBP internal exposure in the Chinese population should be reduced. The ic-ELISA method has been proved as a cost effective, specific, and highly sensitive screening tool to detect DBP in urinary samples.