Search results for "Ototoxicity"
showing 10 items of 42 documents
Pyrrolo[2,3-h]quinolinones: A new ring system with potent photoantiproliferative activity
2006
A new class of compounds, the pyrrolo[2,3-h]quinolin-2-ones, nitrogen isosters of the angular furocoumarin Angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents with increased antiproliferative activity and lower undesired toxic effects than the lead compound. Two synthetic pathways were approached to allow the isolation both of the dihydroderivatives 10-17 and of the aromatic ring system 23. Compounds 10-17 showed a remarkable phototoxicity and a great UVA dose dependence reaching IC(50) values at submicromolar level. Intracellular localization of these compounds has been evaluated by means of fluorescence microscopy using tetramethylrhodamine methyl ester a…
Release of Inflammatory Mediators (PGE2, IL-6) by Fenofibric Acid-Photosensitized Human Keratinocytes and Fibroblasts
1998
Ultraviolet-A radiation has weak effects on the release of inflammatory mediators by skin cells due to the poor overlap between UVA wavelengths and the absorption spectra of the relevant chromophores of key biomole-cules. However, this situation could be very different in the presence of a photosensitizing drug. To investigate this issue, we have irradiated human skin cells (keratinocytes and fibroblasts) in the presence of fenofibric acid (the active phototoxic metabolite of fenofibrate). The results of this research show a dual effect on the production/release of inflammatory mediators: the synthesis of the proinflammatory cytokine interleukin-6 becomes strongly inhibited at photosensitiz…
Effect of?-cyclodextrin complexation on the photohaemolitic activity induced by Ketoprofen and Naproxen sensitization
1993
Red blood cell lysis photosensitized by two non-steroidal anti-inflammatory drugs Naproxen (NAP) and Ketoprofen (KPF) was investigated in the presence of β-cyclodextrin (β-Cyd). The photohaemolysis was inhibited by the addition of β-Cyd both for NAP and, to a lesser extent, for KPF. The protective action was found only in a restricted range of concentration of β-Cyd. Higher amounts of β-Cyd interfered with the resistance of the cell to the osmotic shock induced by the photosensitization process. The complexing action of β-Cyd was ascertained through UV-vis absorption spectroscopy, induced circular dichroism and emission spectroscopy. The isolated complexes Naproxen-β-Cyd (NAP-β-Cyd) and Ket…
Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses
2012
BACKGROUND AND PURPOSEExposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM)-treated animals and cultures.EXPERIMENTAL APPROACHWistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro-inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats.KEY RESULTSD…
Cis-diaminedichloro platinum ototoxicity. An experimental study.
1985
Four groups of guinea pigs received different doses of cis-platinum. SEM and TEM showed a direct relation between the dose and the damage. The first row of OHC is the first one to be damaged. The IHC are more resistant than the OHC. The pattern of destruction is similar to the one produced by the aminoglucoside antibiotics.
Exposure to ototoxic agents and hearing loss: A review of current knowledge
2014
Several experimental and clinical studies have shown that a variety of ototoxic agents (such as drugs, industrial chemicals and noise) can cause sensorineural hearing loss. The most common ototoxic drugs used in clinical practice include: aminoglycoside and macrolide antibiotics, quinoline anti-malarials, platinum analog antineoplastics, loop diuretics, and acetylsalicylic acid. Among chemical agents with potential ototoxic properties are: organic solvents, heavy metals, organotins, nitriles, asphyxiants, and pesticides/herbicides. Acoustic exposure to high intensity and/or prolonged noise can also cause permanent threshold shifts in auditory perception. Ototoxic agents can influence audito…
Modulation of Efficient Diiodo-BODIPY in vitro Phototoxicity to Cancer Cells by Carbon Nano-Onions
2020
Photodynamic therapy (PDT) is currently one of the most promising approaches for targeted cancer treatment. It is based on responses of vital physiological signals, namely reactive oxygen species (ROS), which are associated with diseased condition development, such as tumors. This study presents the synthesis, incorporation, and application of a diiodo-BODIPY based photosensitizer, based on a non-covalent functionalization of carbon nano-onions (CNOs). In vitro assays demonstrate that HeLa cells internalize the diiodo-BODIPY molecules, and their CNOs nanohybrids. Upon cell internalization and light exposure, the pyrene-diiodo-BODIPY molecules induce an increase of the ROS level of HeLa cell…
Synthesis, characterization, and cellular investigations of porphyrin– and chlorin–indomethacin conjugates for photodynamic therapy of cancer
2021
Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin- and chlorin-indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by 1H, 19F and 13C NMR as well as by high resolut…
Phytochemical profile and phototoxicity of eleven Hypericum species extracts
2017
The genus Hypericum (family Hypericaceae) contains 484 species, one of which, Hypericum perforatum, is largely used in medicine as antidepressant, as well as antinflammatory, and antimicrobial agent. Hypericin, together with the other naphthodianthrone derivatives named hypericins (the red pigments recognized as partially responsible for biological activities of this plant), has been identified largely in more than 300 Hypericum species (Skalkos et al., 2006). Particularly, hypericins are one of the most potent naturally occurring photodynamic agents; indeed, upon light irradiation, they very effectively induce apoptosis and/or necrosis of cancer cells (Karioti et al., 2010) and thus might …
Photochemotherapeutic heterocyclic agents having antiproliferative and antineoplastic activity
2012
The present invention concerns the synthesis of new analogs of angelicins, pyrrolo[3,2-h]quinoline, for the treatment of pathologie having hyperproliferative character including those having neoplastic nature. The treatment is based on the combined action of pyrrolo[3,2-h]quinolines and UV-A light, through a clinical approach defined as PUVA (psoralen-UVA light). The most important feature of these compounds is that they exert their remarkable phototoxicity without any DNA damage, which is the main origin of the side effects of the PUVA therapy