linoleic-acid and tiaprofenic-acid

A careful study of the linoleic acid hydroperoxide (LOOH) profile obtained upon peroxidation of linoleic acid (LA) photosensitized by tiaprofenic acid (TPA) and analogous ketones has been undertaken to distinguish between type-I and type-II photoperoxidation mechanisms. 1,4-Cyclohexadiene and 1,2-dimethylcyclohexa-2,5-dienecarboxylic acid (CHDCA) have also been used as models for LA since they also have double allylic systems. Coirradiation of LA with TPA and decarboxytiaprofenic acid (DTPA) in acetonitrile and micellar media produced significant amounts of conjugated dienic LOOH. The cis,trans to trans,trans ratio depended on the irradiation time; thus, this parameter is an ambiguous tool for mechanistic assignment. An interesting finding was the decrease of the LOOH level after long irradiation times in mixtures photooxidized by DTPA, which is attributed to quenching of the DTPA triplet by the generated dienic LOOH. High-performance liquid chromatography analyses confirmed that the main pathway operating in photodynamic lipid peroxidation sensitized by (D)TPA is a type-I mechanism. However, product studies using CHDCA have clearly shown that a type-II mechanism is also operating and might contribute to the overall photooxidation process in a significant way.

Topics: Carboxylic Acids; Chromatography, High Pressure Liquid; Cyclohexanes; Cyclohexenes; Isomerism; Linoleic Acid; Lipid Peroxidation; Models, Chemical; Molecular Structure; Photosensitizing Agents; Propionates

Analysis of the photomixtures resulting from irradiation of aqueous solutions of linoleic acid sensitized by tiaprofenic acid (TPA) or its major photoproduct (DTPA) by HPLC has shown the formation of all the four possible conjugated dienic hydroperoxides. According to laser flash photolysis experiments the rate constants for hydrogen abstraction from linoleic acid by the excited triplet states of TPA and DTPA are 2 x 10(5) and 3.2x 10(5) M(-1) s(-1), respectively. These data, together with the known rate constants for oxygen quenching of triplet (D)TPA and for the reaction of singlet oxygen with linoleic acid, show that the mechanism is mixed type I/type II. Finally, typical radical scavengers such as BHA and singlet oxygen quenchers such as DABCO and sodium azide are efficient quenchers of the triplet excited state of DTPA. This shows the risk of assigning mechanisms based on indirect 'evidences' using 'specific' additives.

Topics: Lasers; Linoleic Acid; Lipid Peroxidation; Photolysis; Photosensitizing Agents; Propionates

The photochemistry of the photosensitizing nonsteroidal antiinflammatory drugs tiaprofenic acid and suprofen involves the intermediacy of short-lived species (i.e. radicals). The data obtained in the present work strongly suggest that such intermediates may be responsible for the phototoxicity of 2-arylpropionic acids by inducing photodynamic lipid peroxidation at drug concentrations likely to be reached in the skin. This has been investigated using linoleic acid as a model lipid and determining the amount of hydroperoxides by measuring the spectrophotometric absorption at 233 nm, associated with the formation of dienic hydroperoxides. The major photoproducts of tiaprofenic acid and suprofen are derivatives bearing an ethyl side chain. Photoproducts of this type, due to the lack of polar moieties, are highly lipophilic and likely to accumulate in the lipid bilayer of cell membranes. Taking into account their ability to induce photodynamic lipid peroxidation and their marked photostability, it is conceivable that such photoproducts can participate in many catalytic cycles, playing a significant role in the mechanism of photosensitization by tiaprofenic acid and suprofen.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; In Vitro Techniques; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Male; Photochemotherapy; Photosensitizing Agents; Propionates; Rats; Rats, Sprague-Dawley; Suprofen