Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis

Baralić, Katarina; Živančević, Katarina; Jorgovanović, Dragica; Javorac, Dragana; Radovanović, Jelena; Gojković, Tamara; Djordjević, Aleksandra Buha; Ćurčić, Marijana; Mandinić, Zoran; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

doi:10.1016/j.fct.2021.112325

Cited by 23 publications

(14 citation statements)

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“…The exaggerated effect in the mixed group only might indicate the potential additivity and synergy. This notion was supported by (Baralić, Živančević, et al, 2021) who reported an additive effect of both BPA and DBP combined in the induction of type 2 diabetes via apoptosis and oxidative stress‐mediated mechanisms. In contrast, (Bodin et al, 2015) found no additive effect of the combination of BPA and phthalates in the induction of insulitis and development of diabetes in NOD mice, even the phthalate in combination with BPA has reduced the BPA effects on diabetes development, but not insulitis development.…”

Section: Discussionmentioning

confidence: 70%

“…In accordance, (Bodin et al, 2015) reported no effect of phthalate (including DBP) on diabetes development. On the other hand, (Baralić, Živančević, et al, 2021) conducted a toxicogenomic analysis study and reported several genes linked to diabetes type 2 and mutual for BPA and DBP. Also, (Majeed et al, 2021) reported that hyperglycemia and insulin resistance, in rats could be attributed to DBP exposure.…”

Section: Discussionmentioning

confidence: 99%

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Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol‐A versus dibutyl phthalate is mediated by HSP60/caspase‐3 expression in male albino rats

Morsi

Mersal

Alsabih

et al. 2022

Cell Biology International

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Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products.Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylin & eosin (H & E) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by H & E changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction.However, rats exposed to DBP alone showed no changes in either α or β-cells. Both combined-exposed animals displayed α and β apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in αcell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/β cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol‐A versus dibutyl phthalate is mediated by HSP60/caspase‐3 expression in male albino rats

Morsi

Mersal

Alsabih

et al. 2022

Cell Biology International

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“…Another interesting aspect of this study is the evaluation of co-exposure to DEHP and BPA in women; indeed, the concentrations of these plasticizers were positively correlated, in particular in Central and Southern Italy, suggesting possible common sources or an extensive use of plastics, resulting in a consequent cumulative exposure. This evidence is particularly relevant, considering the effects exerted by the mixture on the glucose metabolism, thyroid and cancer development exerted by the mixture and shown in in vivo studies (Baralic et al, 2021; Lin et al, 2011; Zhang et al, 2021; Zhang et al, 2022). In addition, the combined exposure of juvenile rats to DEHP and BPA, at same doses recorded in this HBM study, was associated to synergic action in the metabolic system and antagonism action in the reproductive and endocrine systems (Tassinari et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Women exposure to Di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA) from different residing areas in Italy: data from the LIFE PERSUADED project

Carli

Tait

Busani

et al. 2022

Preprint

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Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors. In the frame of the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di (2-ethylhexyl) phthalate (DEHP) metabolites in 900 Italian women enrolled between 2015 and 2017 and living in North, Centre and South of Italy in both rural and urban areas. The whole cohort, representative of the Italian female adult population, was exposed to DEHP and BPA with measurable levels above the limit of detection (LOD) in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in South compared to Central and Northern Italy and for BPA in Northern compared to Central and Southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary Tolerable Daily Intake of 4 μg/kg per day established by the European Food Safety Authority in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. These results suggest to further limit the exposure to DEHP and BPA through specific legislative measures.

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“…Thus, due to their omnipresence in the environment, a mixture of EDCs, such as DEHP, DBP, and bisphenol A (BPA), has the capability to induce more pronounced effects than those provoked by single substances. Possible additive effects, including synergistic and antagonistic effects, were reported both in vivo and in vitro [ 50 – 53 ]. However, this study did not cover a variety of EDCs, and the effects of the mixture need to be clarified by future studies.…”

Section: Discussionmentioning

confidence: 99%

Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes

Chen

Zhang

Chen

et al. 2021

Journal of Diabetes Research

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Aims. Phthalates, which are recognized environmental endocrine-disrupting chemicals, are associated with thyroid hormone disruption. We aimed to evaluate the relationship of phthalate metabolites with thyroid function and thyroid homeostasis parameters in type 2 diabetes and to explore whether thyroid autoimmunity status and metformin, the most common antidiabetic drug, may influence such associations. Methods. Concurrent urine and blood samples were collected from 639 participants with type 2 diabetes in the METAL (Environmental Pollutant Exposure and Metabolic Diseases in Shanghai) study. We measured urinary concentrations of thirteen phthalate metabolites along with serum levels of thyroid-stimulating hormone (TSH), total T4 and T3, free T4 (FT4) and T3 (FT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). Four parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel’s TSH index (TSHI), and thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Results. Among all participants, after full adjustment, multivariable regression analysis showed that some urine phthalate metabolites were negatively associated with TSH, TSHI, and TTSI levels and positively associated with FT3, T3, SPINA-GD, and SPINA-GT levels. None of the urine phthalate metabolites exhibited a significant association with thyroid autoimmunity. The associations of phthalate metabolites with thyroid function and thyroid homeostasis parameters differed based on thyroid autoantibody and metformin treatment status. Conclusions. Urinary phthalate metabolites may be associated with thyroid function and thyroid homeostasis parameters among participants with type 2 diabetes. Furthermore, our present study suggested that thyroid autoantibody status and metformin treatment status are potential mediators of such associations.

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Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: Merging bioinformatics with in vivo analysis

Cited by 23 publications

References 97 publications

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol‐A versus dibutyl phthalate is mediated by HSP60/caspase‐3 expression in male albino rats

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol‐A versus dibutyl phthalate is mediated by HSP60/caspase‐3 expression in male albino rats

Women exposure to Di(2-ethylhexyl)phthalate (DEHP) and bisphenol A (BPA) from different residing areas in Italy: data from the LIFE PERSUADED project

Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes

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