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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-11-21
pubmed:abstractText
This article describes the results of a coupled photophysical and photobiological study aimed at understanding the phototoxicity mechanism of the antimalarial drugs amodiaquine (AQ), primaquine (PQ) and chloroquine (CQ). Photophysical experiments were carried out in aqueous solutions by steady-state and time-resolved spectrometric techniques to obtain information on the different decay pathways of the excited states of the drugs and on the transient species formed upon laser irradiation. The results showed that all three drugs possess very low fluorescence quantum yields (10(-2)-10(-4)). Laser flash photolysis experiments proved the occurrence of photoionization processes leading to the formation of a radical cation in all three systems. In the case of AQ the lowest triplet state was also detected. Together with the photophysical properties the photobiological properties of the antimalarial drugs were investigated under UV irradiation, on various biological targets through a series of in vitro assays. Phototoxicity on mouse 3T3 fibroblast and human keratinocyte cell lines NCTC-2544 was detected for PQ and CQ but not for AQ. In particular, PQ- and CQ-induced apoptosis was revealed by the externalization of phosphatidylserine. Furthermore, upon UV irradiation, the drugs caused significant variations of the mitochondrial potential (Deltapsi(mt)) measured by flow cytometry. The photodamages produced by the drugs were also evaluated on proteins, lipids and DNA. The combined approaches were useful in understanding the mechanism of phototoxicity induced by these antimalarial drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0031-8655
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1415-27
pubmed:meshHeading
pubmed-meshheading:18028216-Amodiaquine, pubmed-meshheading:18028216-Animals, pubmed-meshheading:18028216-Antimalarials, pubmed-meshheading:18028216-Cell Line, pubmed-meshheading:18028216-Cell Survival, pubmed-meshheading:18028216-Chloroquine, pubmed-meshheading:18028216-DNA, pubmed-meshheading:18028216-DNA Damage, pubmed-meshheading:18028216-Humans, pubmed-meshheading:18028216-Lipid Peroxidation, pubmed-meshheading:18028216-Lysosomes, pubmed-meshheading:18028216-Mice, pubmed-meshheading:18028216-Mitochondria, pubmed-meshheading:18028216-Molecular Structure, pubmed-meshheading:18028216-Photobiology, pubmed-meshheading:18028216-Photochemistry, pubmed-meshheading:18028216-Primaquine, pubmed-meshheading:18028216-Reactive Oxygen Species, pubmed-meshheading:18028216-Salmon, pubmed-meshheading:18028216-Spectrophotometry
pubmed:articleTitle
Photophysical properties and photobiological behavior of amodiaquine, primaquine and chloroquine.
pubmed:affiliation
Dipartimento di Scienze Farmaceutiche, Università di Padova, Padova, Italy. giampietro.viola.1@unipd.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't