Photosensitized membrane damage by lipophilic pterin derivatives

MARIANA VIGNONI; MARIA NOEL URRUTIA; HELENA JUNQUEIRA; NILUKSHA WALALAWELA; ALEXANDER GREER; ROSANGELA ITRI; MAURICIO BAPTISTA; ANDRÉS H. THOMAS

Villa Carlos Paz. Córdoba.

Congreso; XIII Encuentro Latinoamericano de Fotoquímica y Fotobiología.; 2017

Lipid peroxidation process is thought to be involved in countless physiological and pathological events and it can happen by different mechanisms: free radical, enzymatic and photosensitized reactions [1]. Pterins are heterocyclic compounds widespread in nature and have been previously identified as good photosensitizers under UVA irradiation [2,3]. It is known that pterin (Ptr, Figure 1), the parent compound of oxidized pterins, is able to freely cross the phospholipid bilayer but, nevertheless, produces photosensitized membrane damage in large unilamellar vesicles (LUVs) [4]. Therefore new lipophilic pterins (pterins 1 and 2, Figure 1) have been synthesized. Their structure allow them to interclate in lipid biomembrane with a high binding constant. In addition, they absorbe in the UVA region and are able to generate singlet oxygen by photosensitization [5].The aim of this work was to investigate the damage produced on the lipid membranes by these lipophilic pterins when they are irradiated under UVA radiation. Comparision with Ptr were made. LUVs of soybean phosphatidylcholine (SoyPC LUVs) were used as model membrane. LUVs containing a photosensitizer were irradiated with UVA light and different analyses were performed. Conjugated dienes and trienes were determined by absorption at 234 and 270 nm respectively. Peroxidation of SoyPC resulted in an important increase in the rate of conjugated dienes production when using pterins 1 and 2 comparing to Ptr. Other experiments were performed to evaluate the production of hydroperoxides, such as FOX2 assay. Furthermore, giant unilamellar vesicles (GUVs) were used to detect the increase of permeability of the membrane by a photosensitized damage.As a conclusion, steady UVA irradiation of solutions containing pterins 1 or 2 and SoyPC LUVs led to the lipid peroxidation of polyunsaturated fatty acids generating mainly hydroperixides. A higher rate of peroxidation was detected when comparing to Ptr as photosensitizer. Membrane permeability is rapidly increase when using pterins 1 and 2 as photosensitizers on GUVs. Therefore, these new lipophilic pterins are more effective to use as photosensitizers in membrane models then Ptr itself and could be further use in different processes, such as photodynamic inactivation.