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Abstract: In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation.
Keywords: rosmarinic acid, aflatoxin B1, chemopreventive effects, antigenotoxic effects, density functional theory, chemical carcinogen scavenger, toxicology
Published in DiRROS: 03.07.2025; Views: 674; Downloads: 520
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Abstract: We address the mechanism by which organic layers on aluminum substrate hinder the penetration of Cl− toward the metal substrate. Localized corrosion by chlorides on Al and its alloys is a major problem, and organic molecules that form self-assembled monolayers on metal substrates may provide efficient corrosion protection. In one of our previous works, we established experimentally that long-chain n-alkyl carboxylic acids form protective layers against Cl− corrosion on Al substrates. In a different work, we identified, using implicit models of the organic layer and metal substrate, two essential effects by which organic layers hinder the penetration of Cl− ions toward the metal substrate. The first effect is due to the inferior solvation of ions in the organic layer compared to that in an aqueous solvent. The second effect is due to the electric field at the electrochemical interface, and the extent to which it affects the penetration of Cl− depends on the electrode potential and the thickness of the organic layer. Both effects are related to a low dielectric constant of the self-assembled monolayer. In the present study, we continue our investigation and explicitly model the organic monolayer and Al substrate using density-functional-theory calculations. To this end, we consider organic monolayers consisting of either dodecanoic- or hexanoic-acid molecules. Current calculations confirm the findings of the simplified implicit models, i.e. the energy barrier for the Cl− penetration increases with the thickness of the organic monolayer and with Cl− concentration in the monolayer. Furthermore, we propose a new mechanism by which Cl− penetrates the organic monolayer. Due to the considerably inferior solvation of Cl− in the organic layer compared to that in water, calculations suggest that it is energetically easier to locally “open” the organic monolayer by creating a hole large enough to accommodate water molecules and Cl−. The presence of water molecules ensures a stronger Cl− solvation and a better electrostatic screening between anions. While the energy barrier for the Cl− penetration via the local “opening” mechanism is suggested to be smaller than for the penetration of Cl− into dense homogeneous organic monolayer, it is still significant enough to pose a considerable kinetic barrier for the penetration of Cl− from the aqueous solution into the organic monolayer at room temperature.
Keywords: aluminium, chlorides, self-assembled monolayer, localized corrosion, density-functional theory
Published in DiRROS: 29.04.2025; Views: 951; Downloads: 370
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Keywords: methane, halogenation, catalysis, density functional theory, kinetics, mechanism
Published in DiRROS: 16.04.2020; Views: 4181; Downloads: 2164
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