0000000000042858
AUTHOR
Daniel Hernández
Minimal flavour seesaw models
26 pages, 8 figures.-- ArXiv pre-print available at: http://arxiv.org/abs/0906.1461
Mechanisms of photosensitization by drugs: Involvement of tyrosines in the photomodification of proteins mediated by tiaprofenic acid in vitro
The photosensitizing potential of drugs must be related to their photoreactivity towards the target biomolecules. In this context, a representative photosensitizing drug (tiaprofenic acid) was co-irradiated with a model protein, bovine serum albumin (BSA). This led to a significant degree of protein crosslinking and to the formation of trace amounts of drug-BSA photoadducts. Amino acid analysis of the hydrolysed (HC1) protein showed that His and Tyr undergo a dramatic decrease (approx. 90%) as a consequence of drug-mediated photodynamic processes. When the drug was irradiated in the presence of the pure amino acids, extensive phototransformation of the latter was observed. Other photosensit…
Photobinding of Tiaprofenic Acid and Subprofen to Proteins and Cells: A Combined Study Using Radiolabeling, Antibodies and Laser Flash Photolysis of Model Bichromophores
Drug photoallergy is a matter of current concern. It involves the formation of drug-protein photoadducts (photoantigens) that may ultimately trigger an immunological response. Tyrosine residues appear to be key binding sites in proteins. The present work has investigated the photobinding of tiaprofenic and (TPA) and the closely related isomer suprofen (SUP) to proteins and cells by means of radioactive labeling and drug-directed antibodies. To ascertain whether preassociation with the protein may play a role in photoreactivity, two model bichromophoric compounds (TPA-Tyr and SUP-Tyr) have been prepared and studied by laser flash photolysis. The results of this work show that (a) TPA and SUP…
MOLECULAR BASIS OF DRUG PHOTOTOXICITY: PHOTOSENSITIZED CELL DAMAGE BY THE MAJOR PHOTOPRODUCT OF TIAPROFENIC ACID
Tiaprofenic acid is a photosensitizing nonsteroidal anti-inflammatory drug, whose major photoproduct (decarboxytiaprofenic acid) is also a potent photosensitizer. Because of the lack of the carboxylate moiety, this photoproduct is more lipophilic and might bind more efficiently to cell membranes, thereby causing phototoxic damage. To verify the feasibility of this hypothesis, we have prepared the 3H-labeled analogs of tiaprofenic acid and its photoproduct and examined the binding, persistence and phototoxicity of the photoproduct using poorly metabolizing (fibroblasts) and actively metabolizing cells (hepatocytes). The photoproduct of tiaprofenic acid accumulates in both cell types as it is…
Antibodies directed to drug epitopes to investigate the structure of drug-protein photoadducts. Recognition of a common photobound substructure in tiaprofenic acid/ketoprofen cross-photoreactivity.
Drug-induced photoallergy is an immune adverse reaction to the combined effect of drugs and light. From the mechanistic point of view, it first involves covalent binding of drug to protein resulting in the formation of a photoantigen. Hence, determination of the structures of drug-protein photoadducts is of great relevance to understand the molecular basis of photoallergy and cross-immunoreactivity among drugs. Looking for new strategies to investigate the covalent photobinding of drugs to proteins, we generated highly specific antibodies to drug chemical substructures. The availability of such antibodies has allowed us to discriminate between the different modes by which tiaprofenic acid (…
Management and research on plastic debris in Uruguayan Aquatic Systems: update and perspectives
Synthetic plastics have become an indispensable component of modern life, and the amount of plastics disposal has increased dramatically as a result. With human population increasing, it is expected that the prevalence of plastic debris in the environment will also increase, unless sustainable daily habits are incorporated, waste management improved, and new alternative materials are discovered and popularized. To date, several reports show negative effects of plastic debris on marine and freshwater fauna (e.g. invertebrates, birds, turtles, marine mammals). Plastic are ubiquitous in the water column, deposited in fine sediments and enter the guts, respiratory structures and tissues of diff…