Abstract
Although benzophenone-3 (BP-3) has frequently been reported to play a role in endocrine disruption, there is insufficient data regarding the impact of BP-3 on the nervous system, including its possible adverse effects on the developing brain. Our study demonstrated that BP-3 caused neurotoxicity and activated apoptosis via an intrinsic pathway involving the loss of mitochondrial membrane potential and the activation of caspases-9 and -3 and kinases p38/MAPK and Gsk3β. These biochemical alterations were accompanied by ROS production, increased apoptotic body formation and impaired cell survival, and by an upregulation of the genes involved in apoptosis. The BP-3-induced effects were tissue-specific and age-dependent with the most pronounced effects observed in neocortical cells at 7 days in vitro. BP-3 changed the messenger RNA (mRNA) expression levels of Erα, Erβ, Gpr30, and Pparγ in a time-dependent manner. At 3 h of exposure, BP-3 downregulated estrogen receptor mRNAs but upregulated Pparγ mRNA. After prolonged exposures, BP-3 downregulated the receptor mRNAs except for Erβ mRNA that was upregulated. The BP-3-induced patterns of mRNA expression measured at 6 and 24 h of exposure reflected alterations in the protein levels of the receptors and paralleled their immunofluorescent labeling. Erα and Pparγ agonists diminished, but Erβ and Gpr30 agonists stimulated the BP-3-induced apoptotic and neurotoxic effects. Receptor antagonists caused the opposite effects, except for ICI 182,780. This is in line with a substantial reduction in the effects of BP-3 in cells with siRNA-silenced Erβ/Gpr30 and the maintenance of BP-3 effects in Erα- and Pparγ siRNA-transfected cells. We showed for the first time that BP-3-affected mRNA and protein expression levels of Erα, Erβ, Gpr30, and Pparγ, paralleled BP-3-induced apoptosis and neurotoxicity. Therefore, we suggest that BP-3-evoked apoptosis of neuronal cells is mediated via attenuation of Erα/Pparγ and stimulation of Erβ/Gpr30 signaling.
Highlights
The toxicity of ultraviolet light (UV) filters used in sunscreens and cosmetics to attenuate the negative effects of harmful UV radiation on skin and hair has become a concern
We showed for the first time that BP-3affected messenger RNA (mRNA) and protein expression levels of Erα, Erβ, Gpr30, and Pparγ, paralleled BP-3-induced apoptosis and neurotoxicity
In 7 days in vitro (DIV) neocortical cultures, BP-3 (25–100 μM)-induced caspase-3 increased to 160% of the control level at 6 h and was further enhanced to 190% at 24 h post-treatment (Fig. 1a)
Summary
The toxicity of ultraviolet light (UV) filters used in sunscreens and cosmetics to attenuate the negative effects of harmful UV radiation on skin and hair has become a concern. More than approximately 10,000 tons of UV filters are produced annually for the global market [1]. The variety of such compounds and the percentage of different filters added to industrial products are expanding with the increasing demand to prevent UV radiation-induced cell damage. Organic chemicals that absorb UVA (400–315 nm) or UVB (315–280 nm) radiation are added at concentrations of up to 10% to sunscreen products for skin protection. Due to public anxiety regarding skin damage caused by UV light, the use of UV screens is increasing, even though the benefit with respect to the prevention of melanoma remains controversial. In Europe, 28 chemical substances that function as UV filters are approved for use in industry, but the European Commission has reported many of them as hormonally active substances or endocrine-
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
