Protective effect of Aronia melanocarpa juice against acrylamide-induced cellular toxicity.

Acrylamide (AA) a widely used industrial chemical is also formed during food processing by the Maillard reaction, which makes its exposure to humans almost unavoidable. In this study, we used Schizosaccharomyces pombe as a model organism to investigate AA toxicity (10 or 20 mM concentration) in eukaryotes. In S. pombe, AA delays cell growth causes oxidative stress by enhancement of ROS production and triggers excitement of the antioxidant defence system resulting in the division arrest. Aronia fruit contains a variety of health-promoting substances with considerable antioxidant potential. Therefore, Aronia juice supplementation was tested to evaluate its protective effect against AA-derived perturbations of the organism. Cell treatment with several Aronia juice concentrations ranging from 0 to 2% revealed the best protective effect of 1 or 2% Aronia juice solutions. Both chosen Aronia juice concentrations alleviated AA toxicity through the improvement of the antioxidant cell capacity and metabolic activity by their strong ROS scavenging property. Efficiency of Aronia juice cell protection is dose dependent as the 2% solution led to significantly higher cellular defence compared with 1%. Due to the high similarity of biological processes of S. pombe with higher eukaryotes, the protective effect of Aronia juice against AA toxicity might also apply to higher organisms.

Curative Potential of Substances with Bioactive Properties to Alleviate Cd Toxicity: A Review.

Rapid urbanization and industrialization have led to alarming cadmium (Cd) pollution. Cd is a toxic heavy metal without any known physiological function in the organism, leading to severe health threat to the population. Cd has a long half-life (10-30 years) and thus it represents serious concern as it to a great extent accumulates in organs or organelles where it often causes irreversible damage. Moreover, Cd contamination might further lead to certain carcinogenic and non-carcinogenic health risks. Therefore, its negative effect on population health has to be minimalized. As Cd is able to enter the body through the air, water, soil, and food chain one possible way to defend and eliminate Cd toxicities is via dietary supplements that aim to eliminate the adverse effects of Cd to the organism. Naturally occurring bioactive compounds in food or medicinal plants with beneficial, mostly antioxidant, anti-inflammatory, anti-aging, or anti-tumorigenesis impact on the organism, have been described to mitigate the negative effect of various contaminants and pollutants, including Cd. This study summarizes the curative effect of recently studied bioactive substances and mineral elements capable to alleviate the negative impact of Cd on various model systems, supposing that not only the Cd-derived health threat can be reduced, but also prevention and control of Cd toxicity and elimination of Cd contamination can be achieved in the future.

Ascorbic acid mitigates cadmium-induced stress, and contributes to ionome stabilization in fission yeast.

Cadmium is a highly toxic environmental pollutant which through enhancement of reactive oxygen species (ROS) production triggers oxidative stress to the cell. Cell growth, a fundamental feature of all living organisms is closely connected to the cell shape and homeostasis. As these processes largely depend on cell fitness status and environmental conditions we have analyzed, the impact of different cadmium concentrations and the effect of ascorbic acid (ascorbate, AsA) supplementation on cell growth parameters, cell morphology, and ionome balance maintenance in Schizosaccharomyces pombe. We show that cadmium causes membrane lipid peroxidation resulting in cell shape alterations leading to growth impairment and through mineral elements disequilibrium affects ionome homeostasis in a dose- and time-dependent manner. AsA recognized as one of the most prominent antioxidants, when overdosed, displays considerable pro-oxidant activity, though precise dosing of its supplementation is desired. We present here that AsA under efficacious concentration largely improves cell condition affected by cadmium. Although, we clearly demonstrate the beneficial feature of AsA, further studies are required to fully understand its protective nature on cell homeostasis maintenance under conditions of the broken environment.

Pore-formation by adenylate cyclase toxoid activates dendritic cells to prime CD8+ and CD4+ T cells.

The adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis is a bi-functional leukotoxin. It penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its N-terminal adenylate cyclase enzyme domain (~400 residues). In parallel, ~1300 residue-long RTX hemolysin moiety of CyaA forms cation-selective pores and permeabilizes target cell membrane for efflux of cytosolic potassium ions. The non-enzymatic CyaA-AC(-) toxoid, has repeatedly been successfully exploited as an antigen delivery tool for stimulation of adaptive T-cell immune responses. We show that the pore-forming activity confers on the CyaA-AC(-) toxoid a capacity to trigger Toll-like receptor and inflammasome signaling-independent maturation of CD11b-expressing dendritic cells (DC). The DC maturation-inducing potency of mutant toxoid variants in vitro reflected their specifically enhanced or reduced pore-forming activity and K(+) efflux. The toxoid-induced in vitro phenotypic maturation of DC involved the activity of mitogen activated protein kinases p38 and JNK and comprised increased expression of maturation markers, interleukin 6, chemokines KC and LIX and granulocyte-colony-stimulating factor secretion, prostaglandin E2 production and enhancement of chemotactic migration of DC. Moreover, i.v. injected toxoids induced maturation of splenic DC in function of their cell-permeabilizing capacity. Similarly, the capacity of DC to stimulate CD8(+) and CD4(+) T-cell responses in vitro and in vivo was dependent on the pore-forming activity of CyaA-AC(-). This reveals a novel self-adjuvanting capacity of the CyaA-AC(-) toxoid that is currently under clinical evaluation as a tool for delivery of immunotherapeutic anti-cancer CD8(+) T-cell vaccines into DC.