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P Miano

Publications and source records attributed to P Miano.

7 recordsLinked to original sources

Molecular mechanisms of photosensitization XIII: a combined differential scanning calorimetry and DNA photosensitization study in non steroidal antiinflammatory drugs-DNA interaction.

A combined differential scanning calorimetry (DSC) and photosensitization study has been carried out on the interaction of several NSAID on DNA, both from calf thymus and pBR 322 plasmid. The investigated compounds were both non-steroidal anti-inflammatory drugs as well as compounds related to NSAIDs for structural similar properties, to find evidence for their ability to interact with DNA as a function of steric hindrance and polarity of the chemical structures. The considered NSAIDs were diflunisal (DFN, a salicylic derivative), naproxen (NAP), ketoprofen (KPF), suprofen (SPF) and tiaprofenic acid (TIA, arylpropionic acids). The structural criterion used was related to three different aromatic groups, biphenyl, naphthalene and benzophenone (BZP). In fact drug-DNA interaction can be revealed by variations of the enthalpies and temperatures of unfolding of DNA obtained by comparison of calorimetric peaks, where a decrease of the enthalpy is associated with the drug-DNA interaction, by engaging electrostatic bonds. Testing their ability in inducing DNA cleavage when UVA irradiated can evidence the photosensitizing properties of the drug. A good correlation was found between calorimetric and photosensitization studies. From the results obtained it can be reasonably supposed that the photocleavage depends only on the drug molecules bound to DNA.

Animals↗

Molecular mechanism of drug photosensitization: VIII. Effect of inorganic ions on membrane damage photosensitized by naproxen.

The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced photohemolysis was investigated. In order to better understand this effect, these ions were also tested for lipid peroxidation and protein crosslinking, which are among the main processes involved in erythrocyte membrane damage. The overall results support the hypothesis that metal cations act via a redox scavenging of the radicals which are produced on the lipid component of the membrane. This process occurs through hydrogen abstraction operated by photogenerated naproxen radicals. Moreover, copper can also act as a superoxide anion scavenger: its decay is noxious in photohemolysis, whereas it is not in lipid peroxidation. Metal cations, besides, are not able to scavenge protein crosslinking. On the other hand, iodide is able to reduce both processes because it acts as a heavy atom, favoring intersystem crossing to the unreactive triplet state of the drug, thus reducing naproxen photolysis and, as a consequence, the amount of the damaging species produced. This mechanism was supported by luminescence experiments performed in the absence and in the presence of iodide.

Cations, Divalent↗

Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen.

Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.

Animals↗

[Effects of oral glucose load on blood lipids and on platelet function].

Oral glucose tolerance test (OGTT) has been performed on 12 healthy men. Plasma glucose, cholesterol, triglycerides, total lipids, NEFA, and number, adhesiveness and aggregating of platelets have been measured before and during OGTT (at 30, 60, 90, 120, 150 mins). Results demonstrate that OGTT decreases during the 1st hour, increases during the 2nd hour, and brings again to the initial value the platelet aggregation during the 3rd hour. The biphasic trend of platelet aggregation, in comparison with the monophasic OGTT curve, allows us to hypothesize some relationships between platelet aggregation and not only blood glucose concentration but also the activity of some hormones controlling both blood sugar level and platelet function.

Adult↗