Photosensitizing potential of ciprofloxacin at ambient level of UV radiation

被引:80
作者
Agrawal, Neeraj
Ray, Ratan Singh
Farooq, Mohammad
Pant, Aditya Bhushan
Hans, Rajendra Kumar
机构
[1] Ind Toxicol Res Ctr, Photobiol Div, Lucknow, Uttar Pradesh, India
[2] Ind Toxicol Res Ctr, Lucknow, Uttar Pradesh, India
关键词
D O I
10.1562/2006-10-12-RA-1059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ciproffoxacin 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 (O-1(2)), superoxide anion radical (O-2(center dot-)) and hydroxyl radical ((OH)-O-center dot) 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 O-1(2), O-2(center dot-) and (OH)-O-center dot in a concentration and dose-dependent manner. Sodium azide (NaN3) and 1,4-diazabicyclo 2-2-2-octane (DABCO) inhibited the generation Of O-1(2). Superoxide dismutase (SOD) inhibited 90-95% O-2(center dot-) generation. The drug (5-40 mu g 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)-O-center dot radical was further confirmed by using specific quenchers of (OH)-O-center dot 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 mu g 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 mu g 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. Ciprolfoxacin produced ROS by Type I and Type It photodynamic reactions, interacted with nucleic acid moiety and inhibited cell viability. Further, UV-induced photoperoxidation 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.
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页码:1226 / 1236
页数:11
相关论文
共 51 条
  • [1] THE OPTICS OF HUMAN-SKIN
    ANDERSON, RR
    PARRISH, JA
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1981, 77 (01) : 13 - 19
  • [2] The penetration of light through human skin
    Bachem, A
    Reed, CI
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1931, 97 (01): : 86 - 91
  • [3] Mitochondria and plasma membrane as targets of UVA-induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine
    Bastianon, C
    Zanoni, R
    Miolo, G
    Caffieri, S
    Reddi, E
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2005, 37 (04) : 901 - 908
  • [4] Borenfreund E., 1985, J. Tissue Cult. Methods, V9, P7, DOI [10.1007/BF01666038, DOI 10.1007/BF01666038]
  • [5] Impairment of proteasome function upon UVA- and UVB-irradiation of human keratinocytes
    Bulteau, AL
    Moreau, M
    Nizard, C
    Friguet, B
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (11) : 1157 - 1170
  • [6] PHOTODYNAMIC LIPID-PEROXIDATION BY THE PHOTOSENSITIZING NONSTEROIDAL ANTIINFLAMMATORY DRUGS SUPROFEN AND TIAPROFENIC ACID
    CASTELL, JV
    GOMEZLECHON, MJ
    GRASSA, C
    MARTINEZ, LA
    MIRANDA, MA
    TARREGA, P
    [J]. PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1994, 59 (01) : 35 - 39
  • [7] COHEN G, 1977, ALCOHOL ALDEHYDE MET, P403
  • [8] Dahle J, 2003, CANCER RES, V63, P1464
  • [9] Photocarcinogenesis: UVA vs. UVB radiation
    de Gruijl, FR
    [J]. SKIN PHARMACOLOGY AND APPLIED SKIN PHYSIOLOGY, 2002, 15 (05): : 316 - 320
  • [10] Singlet oxygen-induced DNA damage
    DeFedericis, HC
    Patrzyc, HB
    Rajecki, MJ
    Budzinski, EE
    Iijima, H
    Dawidzik, JB
    Evans, MS
    Greene, KF
    Box, HC
    [J]. RADIATION RESEARCH, 2006, 165 (04) : 445 - 451