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Highlights: [•] DINP-exposed toxicity is associated with the overproduction of ROS. [•] Oral exposure to DINP is likely to present hepatic and renal tissue injury. [•] ROS accumulation maybe further causes IL-1 and TNF-α production at increased levels. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chlorpyrifos (CPF) can induce hepatic and renal tissue injury of mice. [•] CPF can induce oxidative damage of hepatic and renal tissue of mice. [•] Vitamin E can protect against the tissue damage induced by CPF. [ABSTRACT FROM AUTHOR]

Millions of people are regularly exposed to ozone, a gas known to contribute significantly to worsening the symptoms of patients with asthma. However, the mechanisms underlying these ozone exacerbation effects are not fully understood. In this study, we examined the exacerbation effect of ozone in OVA-induced asthma mice and tried to demonstrate the protective mechanism of vitamin E (VE). An asthma mouse model was established, and used to identify the exacerbating effects of ozone by assessing cytokine and serum immunoglobulin concentrations, airway leukocyte infiltration, histopathological changes in lung tissues, and airway hyper-responsiveness. We then determined the amount of reactive oxygen species (ROS) accumulated, the extent to which VE induced ROS elimination, and examined the antagonistic effects of VE on the ozone-induced exacerbating effects. This study showed that 1-ppm ozone exposure could exacerbate OVA-induced asthma in mice. More importantly we found that ozone induced oxidative stress in asthmatic airways may lead to the inhibition of Nuclear factor-erythroid 2-related factor 2 (Nrf2), and may subsequently induce even more exaggerated oxidative stress associated with asthma exacerbation. Through VE induced Nrf2 activation and the subsequent increase in Nrf2 target protein expression, this study suggests a novel mechanism for alleviating ozone exacerbated asthma symptoms. [ABSTRACT FROM AUTHOR]

Syringic acid (SA), a natural polyphenol found in fruits and vegetables, is claimed to show notable hepatoprotection. Nevertheless, low solubility and bioavailability hamper the application of SA. This study aimed to investigate the potential of TPGS/F127/F68 mixed polymeric micelles as a sustained and liver-targeting nanocarrier for SA. Herein, the prepared SA-loaded TPGS/F127/F68 mixed polymeric micelles (SA-TPGS-Ms) were spherically-shaped and homogeneously-distributed nanoparticles with high entrapment efficiency (94.67 ± 2.05%) and sustained release. Besides, in-vitro cell culture studies revealed that SA-TPGS-Ms substantially promoted cellular uptake with excellent biocompatibility. After oral administration, SA-TPGS-Ms demonstrated an increased bioavailability (2.3-fold) and delayed in-vivo elimination compared with the free SA. Furthermore, the alleviation of oxidative stress and amelioration of hepatic injury in CCl 4 -induced hepatotoxicity mice further demonstrated the excellent hepatoprotection of SA-TPGS-Ms. Collectively, SA-TPGS-Ms could be a promising nanocarrier for the utilization of SA in functional foods, with enhanced bioavailability and hepatoprotection. Image 1 • Syringic acid-loaded TPGS/F127/F68 micelles (SA-TPGS-Ms) have been developed. • SA-TPGS-Ms realized a controlled and sustained-release with high stability. • SA-TPGS-Ms enhanced cellular internalization coupled with low cytotoxicity. • SA-TPGS-Ms improved oral bioavailability with delayed in-vivo elimination. • SA-TPGS-Ms improved hepatoprotection against CCl 4 -induced hepatotoxicity in mice. [ABSTRACT FROM AUTHOR]

Abstract Diisodecyl phthalate (DIDP) is a new type of phthalate used in the coating of pharmaceutical pills and in plastic food wrappers. This research was conducted to investigate whether DIDP could cause learning and memory impairment in mice, using formaldehyde (FA) to construct a positive control. Behavioral analysis showed that oral administration of 15 mg kg−1·d−1 DIDP combined with inhalation of 1 mg m−3 FA led to learning and memory impairment in mice. Histopathological observations of the brain showed that the pathological alterations in the hippocampi. Detection of testosterone (T) and estradiol (E2) levels in the brain and serum showed that E2 levels were associated with learning and memory disorders. Reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) revealed the increased oxidative stress levels. Detection of caspase-3, NF-κB, the phosphorylated cAMP response-element binding protein (p-CREB) and the brain derived neurotrophic factor (BDNF) showed that the protective effect mediated by BDNF, is reduced. However, some of these effects were blocked by the administration of Vitmin E (VitE, 100 mg kg−1·d−1) or 17β-estradiol (17β-E2, 100 μg kg−1). These data suggest that DIDP may aggravate the FA-exposure-induced learning and memory impairment in mice, and that 17β-E2 could be utilized to avoid these adverse effects. Graphical abstract Image 1 Highlights • DIDP aggravates the FA-exposure-impaired learning and memory via oxidative stress. • DIDP causes learning and memory disabilities in mice by abnormal estradiol levels. • 17β-E2 could be utilized to avoid DIDP-induced learning and memory impairment. [ABSTRACT FROM AUTHOR]

Diisodecyl phthalate (DIDP) is extensively used as an environmentally friendly plasticizer. However, little is known about the adverse effects and the underlying mechanisms of DIDP exposure on immunological diseases. We aimed to determine the role and mechanisms of DIDP exposure in allergic contact dermatitis-like skin lesions. We show that oral DIDP exposure can aggravate allergic dermatitis in mice. Moreover, an increase of ROS, total serum IgE and IL-4 levels were concomitant with this deterioration. We detected the expression of Thymic stromal lymphopoietin (TSLP) and the activation of STATs and NF-κB signal pathways. The data indicated that DIDP in combination with FITC triggers TSLP production. Our results also suggested that DIDP exacerbated the activation of NF-κB signal pathways, with an enhancement in TSLP expression, which potentiated the activation of STATs and the degranulation of mast cells in the skin, and finally exacerbated allergic dermatitis. The study also suggested that melatonin enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic dermatitis. The results demonstrated that DIDP exacerbated allergic dermatitis through oxidative stress and enhanced TSLP production. [ABSTRACT FROM AUTHOR]

Previously, we reported that exposure to diisononyl phthalate (DINP) resulted in cognitive deficits and anxiety in mice (https://doi.org/10.1038/srep14676). Artificial light at night (ALAN) is now recognized as being a potential threat to human health. However, toxicological evidence concerning exposure to a combination of ALAN and DINP in vivo is limited. To this end, mice were orally exposed to different concentrations of DINP for 28 consecutive days, and ALAN (intensity 150 lux, every night for 12 h). The results showed that oxidative stress levels increased with increasing DINP exposure concentrations, which triggered apoptosis (Bcl-2 levels decreased, Bax levels increased), resulting in nerve cell damage and a decline in the learning and memory abilities of mice. The combined effects of ALAN and DINP exposure on the learning ability and memory of mice are more serious than for DINP exposure alone. The antioxidant vitamin E was shown to have a certain antagonistic effect on the oxidative damage caused by ALAN and DINP exposure. These results highlight a previously unknown relationship between exposure to ALAN and DINP-induced learning and memory impairment, and provide evidence that ALAN may be exacerbating the effects of DINP. [Display omitted] • ALAN exacerbates DINP-induced oxidative damage and apoptosis in the hippocampus. • Combined ALAN and DINP exposure on mouse behavior was more seriously than DINP alone. • VitE reduces pathological changes and oxidative stress caused by ALAN and DINP. [ABSTRACT FROM AUTHOR]

Diisononyl phthalate (DINP) is commonly used as a plasticizer in industrial and consumer product applications. Several studies have suggested a possible link between exposure to DINP and the development of allergic asthma, and the synergistic effect of DINP combined with Ovalbumin (OVA) is a possible way to promote an immune response. These findings are still speculative, since there is insufficient evidence to assess the ability of DINP to influence "allergic asthma pathology". This study was designed to determine any effects of OVA/DINP exposure on airway reactivity, particularly when combined with allergen exposure. Experiments to determine these effects were conducted after 15 days of combined exposure and a subsequent challenge with aerosolized ovalbumin for one week. Airway hyper-responsiveness (lung function), lung tissue pathology, cytokines and oxidative stress biomarkers were investigated. We showed that oral exposure to OVA/DINP could induce airway hyper-responsiveness (AHR), and aggravate airway wall remodeling, and that this deterioration was concomitant with increased immunoglobulin-E and Th2 cytokines secretion. The data also demonstrated that DINP could promote oxidative damage in the lung. In summary, this study showed that DINP has an adjuvant effect on allergic asthma affecting lung function, lung histopathology, immune molecules and causes oxidative damage. Image 1 • Exposure to DINP aggravates allergic asthma in Balb/c mice. • Exposure to DINP triggers airway hyper-responsiveness in Balb/c mice. • Exposure to DINP triggers airway remodeling in Balb/c mice. [ABSTRACT FROM AUTHOR]

Dibutyl phthalate (DBP) is a ubiquitous environmental contaminant that at certain levels can be harmful to human health. Although DBP has been widely linked to immunotoxicity, any association between DBP exposure and splenic injury remains unknown. The purpose of this study was to investigate whether DBP exposure can induce splenic injury and the antagonistic effects of two antioxidants, vitamin E (VitE) and curcumin (Cur), on DBP-induced splenic injury. The levels of ROS, GSH, T-AOC, IL-1β, TNF-α, cytochrome C, caspase-8, caspase-9 and caspase-3 in the spleen homogenate of mice were measured. Any histopathological changes in the spleen were observed using H&E and toluidine blue staining. And the morphology of mitochondria was observed using Janus Green B staining. The results indicate that exposure to 50 mg/kg DBP could cause histopathological changes of the spleen and result in inflammation and apoptosis associated with oxidative stress, which may lead to splenic injury in mice. Moreover, both VitE and Cur could antagonize the oxidative stress induced by DBP to reduce splenic injury. These findings help to expand our understanding of DBP-mediated immunotoxicity, and to show that VitE and Cur can alleviate DBP-induced splenic injury and the possible DBP-associated decline in immune function. Image 1 • DBP exposure may lead to splenic injury and the disorderly expression of CD3+ and CD8+ in spleen. • DBP-induced immunotoxicity may be associated with oxidative stress in spleen. • VitE and Cur antagonize the DBP-induced oxidative stress to reduce splenic injury. [ABSTRACT FROM AUTHOR]

Diisononyl phthalate (DIDP) is commonly used as a plasticizer in industrial and consumer products, however, its toxicity remains unclear. This study investigated the possible involvement of oxidative stress in DIDP-induced liver and kidney toxicity. Liver function and kidney function, tissue lesions, oxidative stress biomarkers, inflammatory mediators and apoptosis factors were investigated in this study. The results showed that oral exposure to DIDP induced a marked increase in lever of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urinary nitrogen (UREA) and creatinine (CREA), decrease in albumin (ALB) level, as well as causing hepatic and renal histopathological change. Investigation of the role of oxidative stress pathways showed that DBP exposure could lead to a significant increase in levels of reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB), while a decrease in glutathione (GSH) levels were observed. Administration of vitamin E to DIDP-treated mice restored these biochemical parameters to within normal levels, and resulted in less damage to livers and kidneys. Overall, these results suggest that the oxidative stress pathway is involved in DIDP-induced toxicity. Image 1 [ABSTRACT FROM AUTHOR]