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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]

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]