The exposure to UV filters: Prevalence, effects, possible molecular mechanisms of action and interactions within mixtures.

Substances that can absorb sunlight and harmful UV radiation such as organic UV filters are widely used in cosmetics and other personal care products. Since humans use a wide variety of chemicals for multiple purposes it is common for UV filters to co-occur with other substances either in human originating specimens or in the environment. There is increasing interest in understanding such co-occurrence in form of potential synergy, antagonist, or additive effects of biological systems. This review focuses on the collection of data about the simultaneous occurrence of UV filters oxybenzone (OXYB), ethylexyl-methoxycinnamate (EMC) and 4-methylbenzylidene camphor (4-MBC) as well as other classes of chemicals (such as pesticides, bisphenols, and parabens) to understand better any such interactions considering synergy, additive effect and antagonism. Our analysis identified >20 different confirmed synergies in 11 papers involving 16 compounds. We also highlight pathways (such as transcriptional activation of estrogen receptor, promotion of estradiol synthesis, hypothalamic-pituitary-gonadal (HPG) axis, and upregulation of thyroid-hormone synthesis) and proteins (such as Membrane Associated Progesterone Receptor (MAPR), cytochrome P450, and heat shock protein 70 (Hsp70)) that can act as important key nodes for such potential interactions. This article aims to provide insight into the molecular mechanisms on how commonly used UV filters act and may interact with other chemicals.

The effect of sunscreen 4-methylbenzylidene camphor in different and reproductive models, its bioaccumulation and molecular effects on ligand-receptor interaction, and protein expression.

4-Methylbenzylidene camphor (4-MBC) is a photo-absorbing UV filter prevalently used in cosmetics, which can be absorbed into circulation and cause systemic effects. 4-MBC is continued to be released in the environment despite the growing knowledge about its bioaccumulation and endocrine disrupting effects. Previous reviews have mentioned UV-filter together but this review considers 4-MBC alone, due to its prevalence and concerning health effects. This review considers 4-MBC's potential effects on human health regarding systemic and molecular effects, with the main focus on reproduction. Also, the potential bioaccumulation and interactions with receptor systems such as the oestrogen receptors ß and α, and progesterone receptor are covered. Additionally, previous studies about 4-MBC's effects on mRNA and protein expression, especially in the prostate and the brain are analysed. Furthermore, 4-MBC is reported to act with inflammatory pathways by activating p38 MAPK and NF-κB, leading to the production of inflammatory TNF-α and IL-6. 4-MBC was also found to induce apoptosis and inhibit cell proliferation and DNA repair. In conclusion, 4-MBC has wide-ranging effects in many different models interacting with multiple pathways causing long-term effects even at low doses and this knowledge can guide governmental risk assessment, regulation divisions and chemical industries.

Autophagy activation can partially rescue proteasome dysfunction-mediated cardiac toxicity.

The ubiquitin-proteasome pathway and its functional interplay with other proteostatic and/or mitostatic modules are crucial for cell viability, especially in post-mitotic cells like cardiomyocytes, which are constantly exposed to proteotoxic, metabolic, and mechanical stress. Consistently, treatment of multiple myeloma patients with therapeutic proteasome inhibitors may induce cardiac failure; yet the effects promoted by heart-targeted proteasome dysfunction are not completely understood. We report here that heart-targeted proteasome knockdown in the fly experimental model results in increased proteome instability and defective mitostasis, leading to disrupted cardiac activity, systemic toxicity, and reduced longevity. These phenotypes were partially rescued by either heart targeted- or by dietary restriction-mediated activation of autophagy. Supportively, activation of autophagy by Rapamycin or Metformin administration in flies treated with proteasome inhibitors reduced proteome instability, partially restored mitochondrial function, mitigated cardiotoxicity, and improved flies' longevity. These findings suggest that autophagic inducers represent a novel promising intervention against proteasome inhibitor-induced cardiovascular complications.