Effects induced by η6-p-cymene ruthenium(II) complexes on Langmuir monolayers mimicking cancer and healthy cell membranes do not correlate with their toxicity.

The mechanism of chemotherapeutic action of Ru-based drugs involves plasma membrane disruption and valuable insights into this process may be gained using cell membrane models. The interactions of a series of cytotoxic η6-p-cymene ruthenium(II) complexes, [Ru(η6-p-cymene)P(3,5-C(CH3)3-C6H3)3Cl2] (1), [Ru(η6-p-cymene)P(3,5-CH3-C6H3)3Cl2] (2), [Ru(η6-p-cymene)P(4-CH3O-3,5-CH3-C6H2)3Cl2] (3), and [Ru(η6-p-cymene)P(4-CH3O-C6H4)3Cl2] (4), were examined using Langmuir monolayers as simplified healthy and cancerous outer leaflet plasma membrane models. The cancerous membrane (CM1 and CM2) models contained either 40 % 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 30 % cholesterol (Chol), 20 % 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and 10 % 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS). Meanwhile, the healthy membrane (HM1 and HM2) models were composed of 60 % DPPC or DOPC, 30 % Chol and 10 % DPPE. The complexes affected surface pressure isotherms and decreased compressional moduli of cancerous and healthy membrane models, interacting with the monolayers headgroup and tails according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). However, the effects did not correlate with the toxicity of the complexes to cancerous and healthy cells. Multidimensional projection technique showed that the complex (1) induced significant changes in the CM1 and HM1 monolayers, though it had the lowest cytotoxicity against cancer cells and is not toxic to healthy cells. Moreover, the most toxic complexes (2) and (4) were those that least affected CM2 and HM2 monolayers. The findings here support that the ruthenium complexes interact with lipids and cholesterol in cell membrane models, and their cytotoxic activities involve a multifaceted mode of action beyond membrane disruption.

The Role of the Ecotoxicology Applied to Seafood as a Tool for Human Health Risk Assessments Concerning Polycyclic Aromatic Hydrocarbons.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants routinely detected in aquatic ecosystems. It is, therefore, necessary to assess the link between deleterious marine biota PAH effects, especially in commercialized and consumed animals, environmental health status, and potential human health risks originating from the consumption of contaminated seafood products. Thus, this review seeks to verify the relationships of ecotoxicological studies in determining effect and safety concentrations on animals routinely consumed by humans. METHODS: A total of 52 published studies between 2011 and 2021, indexed in three databases, were selected following the PICO methodology, and information on test animals, evaluated PAH, and endpoints were extracted. RESULTS: Benzo(a)pyrene and phenanthrene were the most investigated PAHs in terms of biomarkers and test organisms, and mussels were the most evaluated bioindicator species, with an emphasis on reproductive responses. Furthermore, despite the apparent correlation between environmental PAH dynamics and effects on aquatic biota and human health, few assessments have been performed in a multidisciplinary manner to evaluate these three variables together. CONCLUSIONS: The links between human and environmental sciences must be strengthened to enable complete and realistic toxicity assessments as despite the application of seafood assessments, especially to mussels, in bioassays, the connection between toxicological animal responses and risks associated with their consumption is still understudied.