Document Detail


Photosensitizing potential of ciprofloxacin at ambient level of UV radiation.
MedLine Citation:
PMID:  17880519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ciprofloxacin is a widely used fluoroquinolone drug with broad spectrum antibacterial activities. Clinical experience has shown incidences of adverse effects related to skin, hepatic, central nervous system, gastrointestinal and phototoxicity. India is a tropical country and sunlight is abundant throughout the day. In this scenario exposure to ambient levels of ultraviolet radiation (UV-R) in sunlight may lead to harmful effects in ciprofloxacin users. Phototoxicity assessment of ciprofloxacin was studied by two mouse fibroblast cell lines L-929 and NIH-3T3. Generation of reactive oxygen species (ROS) like singlet oxygen (1O2), superoxide anion radical (O2*-) and hydroxyl radical (*OH) was studied under the exposure of ambient intensities of UV-A (1.14, 1.6 and 2.2 mW cm(-2)), UV-B (0.6, 0.9 and 1.2 mW cm(-2)) and sunlight (60 min). The drug was generating 1O2, O2*- and *OH in a concentration and dose-dependent manner. Sodium azide (NaN3) and 1,4-diazabicyclo 2-2-2-octane (DABCO) inhibited the generation of 1O2. Superoxide dismutase (SOD) inhibited 90-95% O2*- generation. The drug (5-40 microg mL(-1)) was responsible for linoleic acid peroxidation. Quenching study of linoleic acid peroxidation with SOD (25 and 50 U mL(-1)) confirms the involvement of ROS in drug-induced lipid peroxidation. The generation of *OH radical was further confirmed by using specific quenchers of *OH such as mannitol (0.5 M) and sodium benzoate (0.5 M). 2'-deoxyguanosine (2'-dGuO) assay and linoleic acid peroxidation showed that ROS were mainly responsible for ciprofloxacin-sensitized photo-degradation of guanine base. L-929 cell line showed 29%, 34% and 54% reduced cell viability at higher drug concentration (300 microg mL(-1)) under UV-A, UV-B and sunlight, respectively. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in NIH-3T3 cell line at higher drug concentration (300 microg mL(-1)) showed a decrease in cell viability by 54%, 56% and 59% under UV-A, UV-B and sunlight, respectively. Results of neutral red uptake assay (NRU) in L-929 cell line were in accordance with MTT assay. The NIH-3T3 cell line showed a higher photosensitizing potential than L-929. The phototoxicity end point shows a time- and concentration-dependent statistically significant (P<0.001) damage. Ciprofloxacin produced ROS by Type I and Type II photodynamic reactions, interacted with nucleic acid moiety and inhibited cell viability. Further, UV-induced photo-peroxidation of linoleic acid accorded the involvement of ROS in the manifestation of drug phototoxicity. Appearance of ciprofloxacin-induced phototoxicity at the ambient level of sunlight is a real risk for the people of India and for those of other tropical countries. We suggest that sunlight exposure should be avoided (especially peak hours) during ciprofloxacin treatment.
Authors:
Neeraj Agrawal; Ratan Singh Ray; Mohammad Farooq; Aditya Bhushan Pant; Rajendra Kumar Hans
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  83     ISSN:  0031-8655     ISO Abbreviation:  Photochem. Photobiol.     Publication Date:    2007 Sep-Oct
Date Detail:
Created Date:  2007-09-20     Completed Date:  2008-01-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1226-36     Citation Subset:  IM    
Affiliation:
Photobiology Division, Industrial Toxicology Research Centre, M.G. Marg, Lucknow, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Ciprofloxacin / pharmacology*
Dose-Response Relationship, Radiation
Mice
Photosensitizing Agents / pharmacology*
Superoxide Dismutase / metabolism
Superoxides / metabolism
Ultraviolet Rays*
Chemical
Reg. No./Substance:
0/Photosensitizing Agents; 11062-77-4/Superoxides; 85721-33-1/Ciprofloxacin; EC 1.15.1.1/Superoxide Dismutase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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