Dietary Linolenic Acid Increases Sensitizing and Eliciting Capacities of Cow's Milk Whey Proteins in BALB/c Mice.

α-Lactalbumin (BLA) and ß-lactoglobulin (BLG) are the major whey proteins causing allergic reactions. Polyunsaturated fatty acids (PUFAs) stand among the extrinsic factors of the food matrix that can bind BLA and BLG and change their bioactivities, but their contribution to change the allergenic properties of these proteins has not been investigated. Here, we aimed to determine how PUFAs influence BLA and BLG to sensitize and trigger allergic responses in BALB/c mice. First, tricine-SDS-PAGE and spectroscopic assays identified that α-linolenic acid (ALA, as a proof-of-concept model) can induce BLA and BLG to form cross-linked complexes and substantially modify their conformation. Then, BALB/c mice (n = 10/group) were orally sensitized and challenged with BLA and BLG or ALA-interacted BLA and BLG, respectively. Allergic reactions upon oral challenge were determined by measuring clinical allergic signs, specific antibodies, levels of type-1/2 cytokines, the status of mast cell activation, and percentage of cell populations (B and T cells) in different tissues (PP, MLN, and spleen). Overall, systemic allergic reaction was promoted in mice gavage with ALA-interacted BLA and BLG by disrupting the Th1/Th2 balance toward a Th2 immune response with the decreased number of Tregs. Enhanced induction of Th2-related cytokines, as well as serum-specific antibodies and mast cell activation, was also observed. In this study, we validated that ALA in the food matrix promoted both the sensitization and elicitation of allergic reactions in BALB/c mice.

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug.

The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.

Quantification of synergistic, additive and antagonistic effects of aerosol components on total oxidative potential.

The interaction-based oxidative potential (OPint) represents the prediction of binary mixture effects distinguishing from linear additivity by including information on binary mixtures among PM components. The objective of this work is to develope a reliable estimate on the possible synergistic or antagonistic possibility of binary PM components and to quantify the combined effect. We firstly assessed the interactions among PM components in generating the OP based on DTT consumption rate and AA depletion. We started with the standard solution sequence (from 0.005 to 10 µM), including quinones (PQ, 1,2-NQ, and 1,4-NQ) and metals (Cu, Mn, and Fe). The interactions between metals were antagonistic interactions in DTT consumption. Cu showed antagonistic interaction with PQ, but additive with 1,2-NQ and 1,4-NQ. Mn interacted synergistically with 1,4-NQ in DTT consumption but antagonistically with PQ (where CPQ < 2.5 µM) and 1,4-NQ (where CPQ < 2 µM). Fe showed synergistic with quinones in investigated concentration range (from 0.01 to 5 µM). Finally, applying a moderate approach, on the basis of interaction magnitude (M = 5), resulted in 1-17% higher environmental risks, compared with the classical calculation method using simple addition. This work highlights a new approach to quantify the interaction effects between metals and quinones in PM components, and apportioning the components' contributions for PM OP.