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1.
Environ Sci Pollut Res Int ; 29(49): 73648-73674, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36083363

RESUMO

The continuous use of household and personal care products (HPCPs) produces an immense amount of chemicals, such as parabens, bisphenols, benzophenones and alkylphenol ethoxylates, which are of great concern due to their well-known endocrine-disrupting properties. These chemicals easily enter the environment through man-made activities, thus contaminating the biota, including soil, water, plants and animals. Thus, on top of the direct exposure on account of their presence in HPCPs, humans are also susceptible to secondary indirect exposure attributed to the ubiquitous environmental contamination. The aim of this review was therefore to examine the sources and occurrence of these noteworthy contaminants (i.e. parabens, bisphenols, benzophenones, alkylphenol ethoxylates), to summarise the available research on their environmental presence and to highlight their bioaccumulation potential. The most notable environmental contaminants appear to be MeP and PrP among parabens, BPA and BPS among bisphenols, BP-3 among benzophenones and NP among alkylphenols. Their maximum detected concentrations in the environment are mostly in the range of ng/L, while in human tissues, their maximum concentrations achieved µg/L due to bioaccumulation, with BP-3 and nonylphenol showing the highest potential to bioaccumulate. Finally, of another great concern is the fact that even the unapproved parabens and benzophenones have been detected in the environment.


Assuntos
Cosméticos , Disruptores Endócrinos , Compostos Benzidrílicos , Benzofenonas/análise , Humanos , Parabenos/análise , Fenóis , Solo , Água
2.
Chemosphere ; 303(Pt 1): 134824, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35525453

RESUMO

The everyday use of household and personal care products (HPCPs) generates an enormous amount of chemicals, of which several groups warrant additional attention, including: (i) parabens, which are widely used as preservatives; (ii) bisphenols, which are used in the manufacture of plastics; (iii) UV filters, which are essential components of many cosmetic products; and (iv) alkylphenol ethoxylates, which are used extensively as non-ionic surfactants. These chemicals are released continuously into the environment, thus contaminating soil, water, plants and animals. Wastewater treatment and water disinfection procedures can convert these chemicals into halogenated transformation products, which end up in the environment and pose a potential threat to humans and wildlife. Indeed, while certain parent HPCP ingredients have been confirmed as endocrine disruptors, less is known about the endocrine activities of their halogenated derivatives. The aim of this review is first to examine the sources and occurrence of halogenated transformation products in the environment, and second to compare their endocrine-disrupting properties to those of their parent compounds (i.e., parabens, bisphenols, UV filters, alkylphenol ethoxylates). Albeit previous reports have focused individually on selected classes of such substances, none have considered the problem of their halogenated transformation products. This review therefore summarizes the available research on these halogenated compounds, highlights the potential exposure pathways, and underlines the existing knowledge gaps within their toxicological profiles.


Assuntos
Cosméticos , Disruptores Endócrinos , Parabenos , Plásticos , Água
3.
J Med Chem ; 64(11): 7809-7838, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34043358

RESUMO

We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/química , Adjuvantes Imunológicos/química , Proteína Adaptadora de Sinalização NOD2/agonistas , Acetilmuramil-Alanil-Isoglutamina/metabolismo , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Adjuvantes Imunológicos/metabolismo , Adjuvantes Imunológicos/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Linhagem Celular , Desenho de Fármacos , Humanos , Imunoglobulina G/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipossomos/química , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteína Adaptadora de Sinalização NOD2/metabolismo , Ovalbumina/imunologia , Relação Estrutura-Atividade , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/citologia , Células Th2/imunologia , Células Th2/metabolismo
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