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Bisphenol A (BPA) is one of the most common worldwide chemicals involved in the industry of polycarbonate plastics, medical devices, and pharmaceuticals. Forty three-month-old albino rats were randomly classified into four groups. Group Ӏ received a daily corn oil dose (5 mL/kg/ body weight, BW) through a gastric tube for one month, Group ӀӀ received a daily dose of Curcumin (200 mg/kg body weight (B.W.) through a gastric tube for one month, Group ӀӀӀ received a daily dose of BPA (0.5 μg/kg B.W.) through a gastric tube for one month and Group ӀV received concomitant daily doses of Bisphenol A and Curcumin as the regimen described in groups ӀӀ and ӀӀӀ. The rats were sacrificed, and glandular portion of stomach was dissected and processed for light, immunohistochemical and ultrastructural study. BPA induced destructed gastric glands, dilated congested blood vessels, submucosal oedema, decreased PAS-positive reactivity, increased collagen fibres deposition, decrease in the positive BCL2 immunoexpression, increased positive PCNA immunoexpression, reduction in the gastric mucosal height and destructive changes in the enteroendocrine, chief and parietal cells. Curcumin coadministration provoked an obvious improvement in the gastric structure. BPA exposure has toxic effects on the glandular portion of the stomach in rats. Otherwise, Curcumin coadministration has exhibited protective impact on the architecture of the stomach. [ABSTRACT FROM AUTHOR]

Bisphenols, synthetic organic compounds used in the production of plastics, are an extremely abundant class of Endocrine Disrupting Chemicals, i.e., exogenous chemicals or mixtures of chemicals that can interfere with any aspect of hormone action. Exposure to BPs can lead to a wide range of effects, and it is especially dangerous if it occurs during specific critical periods of life. Focusing on the perinatal exposure to BPA or its largely used substitute BPS, we investigated the effects on anxiety-related behaviors and the serotonergic system, which is highly involved in controlling these behaviors, in adult mice. We treated C57BL/6J dams orally with a dose of 4 μg/kg body weight/day (i.e., EFSA TDI) of BPA or BPS dissolved in corn oil or with vehicle alone, at the onset of mating and continued treatment until the offspring were weaned. Adult offspring of both sexes performed the elevated plus maze and the open field tests. Then, we analyzed the serotonergic system in dorsal (DR) and median (MnR) raphe nuclei by immunohistochemical techniques. Behavioral tests highlighted alterations in BPA- and BPS-treated mice, suggesting different effects of the bisphenols exposure on anxiety-related behavior in males (anxiolytic) and females (anxiogenic). The analysis of the serotonergic system highlighted a sex dimorphism in the DR only, with control females showing higher values of serotonin immunoreactivity (5-HT-ir) than control males. BPA-treated males displayed a significant increase of 5-HT-ir in all analyzed nuclei, whereas BPS-treated males showed an increase in ventral DR only. In females, both bisphenols-treated groups showed a significant increase of 5-HT-ir in dorsal DR compared to the controls, and BPA-treated females also showed a significant increase in MnR.These results provide evidence that exposure during the early phases of life to BPA or BPS alters anxiety and the raphe serotonergic neurons in a sex-dependent manner. [Display omitted] • Exposure to low-dose bisphenol A or S during the perinatal period represents a risk to the developing organism. • Anxiety-related behaviors are altered in bisphenol A or S-exposed mice. • Serotonergic system within dorsal and median raphe nuclei is altered in bisphenol A or S exposed mice. • Perinatal exposure to bisphenol A or S affected differentially the two sexes. • New and more stringent regulations on the use of BPA and its analogue BPS are needed. [ABSTRACT FROM AUTHOR]

Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis). [Display omitted] • Oxidative stress and inflammation – the most important mechanisms. • Changes in rat liver – most prominent/present only in the MIX group. • Redox status and bioelements changes – most prominent/present only in the MIX group. • Zebrafish: DBP in binary mixtures – lethal outcome at two highest concentrations. • Zebrafish: hepatotoxicity of DEHP/DBP/BPA mixture dictated by BPA. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 108 CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue. [Display omitted] • MIX (DEHP + DBP + BPA): 24 mutual genes connected with asthma development. • Apoptosis, inflammation and oxidative stress – the most probable mechanisms. • Redox status and bioelements changes – most prominent/present only in the MIX group. • Multi-strain probiotic bound 29.25, 29.04 and 41.75% for DEHP, DBP and BPA. • Probiotic mitigated MIX-induced changes in rat lung, thymus and kidney tissue. [ABSTRACT FROM AUTHOR]