Search results for "Ototoxicity"
showing 10 items of 42 documents
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…
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.
Intra- and extra-cellular DNA damage by harmine and 9-methyl-harmine
2014
It is known that b-carbolines are able to produce photosensitized damage in cell-free DNA, but there is little information on their effects on cellular DNA. Therefore, we have analyzed the DNA damage produced by harmine and 9-methyl-harmine under UVA irradiation in V79 cells, together with the associated generation of micronuclei and photocytotoxicity. The results indicate that the most frequent photoproducts generated in the cellular DNA are modified purines such as 8-oxo-7,8-dihydroguanine. Only relatively few single-strand breaks were observed. CPDs were absent, although they were generated in cell-free DNA irradiated under the same conditions. The overall extent of DNA damage in the cel…
Photoinduced lethal and sublethal toxicity of retene, a polycyclic aromatic hydrocarbon derived from resin acid, to coregonid larvae
2004
A comparative investigation on the acute phototoxicity of retene to vendace (Coregonus albula) and whitefish (C. lavaretus), both having pelagial larvae in spring, was conducted. To test the concept of early warning of sublethal biomarkers in relation to lethality to posthatch stages, we examined the effects of ultraviolet-B (UV-B) and retene on the levels of cytochrome P4501A (CYP1A) and heat shock protein 70 (HSP70) by exposing the animals to elevated levels of these factors for 48 and 72 h, respectively. Whereas UV-B and retene on their own were not lethal, simultaneous retene and UV-B exposure caused very high mortality to both species. The median lethal concentration (LC50; i.e., the c…
High sensitivity of northern pike larvae to UV-B but no UV-photoinduced toxicity of retene
2003
In order to investigate whether increased UV-B radiation is a risk factor, a series of acute laboratory experiments was conducted with larval stages of the northern pike (Esox lucius L.), hatching in Nordic waters in May. Further, a comparative investigation on the acute phototoxicity of retene (7-isopropyl-1-methylphenanthrene), a PAH compound recently revealed to posses UV-B-induced phototoxicity in larval coregonids, was conducted with pike larvae. In semi-static experiment, larvae were pre-exposed to retene (3, 9, 30 and 82 microg/g), with relevant controls, for 24 h and then irradiated for 3 h once a day (two consecutive days) with three UV-B doses (CIE-weighted 1.0, 1.8 or 2.7 kJ/m2 p…
Long-Term Results after Interval Therapy with Intratympanic Gentamicin for Meni??re???s Disease
2004
Objectives The new single-shot and interval treatment for Meniere's disease with gentamicin was designed to avoid cochlear damage during treatment with gentamicin. Methods To date, 90 patients were treated with the single-shot or interval gentamicin therapy. Fifty-seven cases of Meniere's disease were followed up prospectively between 2 and 4 years. During one treatment series, a maximum of three intratympanic gentamicin injections within 15 days were applied, each consisting of 0.3 mL (12 mg) of gentamicin (days 1, 8, and 15). Thirty of these 57 patients (53%) needed only one injection to be controlled (single-shot treatment). Results Vertigo attacks were completely controlled in 95% and p…
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 …
Different sensitivities of whitefish (Coregonus lavaretus) and northern pike (Esox lucius) eleutheroembryos to photoinduced toxicity of polycyclic ar…
2011
The photoinduced toxicity of two polycyclic aromatic hydrocarbons (PAHs), retene (RET) and pyrene (PYR), to the eleutheroembryos of whitefish and northern pike was studied. Fish were exposed to three concentrations of RET and PYR, and irradiated with ultraviolet radiation (UVR) or visible light for 3 h on two consecutive days. UVR covered the absorption maxima of RET and PYR at UVB and UVA, the daily UVR doses were 30 and 28 kJ m−2, respectively. After 72 h, mortality and behavioral abnormalities were observed. Survivors were analyzed for the proteins of CYP1A, CYP3A, Hsp70, and the activity of glutathione reductase (GR). While neither PAHs nor UVR on their own were lethal, simultaneous exp…
MOLECULAR BASIS OF DRUG PHOTOTOXICITY: PHOTOSENSITIZED CELL DAMAGE BY THE MAJOR PHOTOPRODUCT OF TIAPROFENIC ACID
1994
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…
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…