PMID- 24286391
OWN - NLM
STAT- MEDLINE
DCOM- 20141201
LR  - 20140207
IS  - 1029-2470 (Electronic)
IS  - 1029-2470 (Linking)
VI  - 48
IP  - 3
DP  - 2014 Mar
TI  - Cellular and molecular mechanism of ofloxacin induced apoptotic cell death under 
      ambient UV-A and sunlight exposure.
PG  - 333-46
LID - 10.3109/10715762.2013.869324 [doi]
AB  - Ofloxacin (OFLX) is a racemic mixture of levofloxacin which revealed 
      phototoxicity in patients exposed with sunlight after medication. Here, we have 
      been addressed the possible cellular and molecular mechanisms of OFLX induced 
      apoptosis under ambient UV-A and sunlight exposure using HaCaT cell line as a 
      model. The results showed that Photodegradation and three photo-products 
      formation of OFLX by LC-MS/MS under ambient intensities of UV-A (1.5 and 2.2 
      mW/cm(2)) and sunlight. OFLX produced (1)O2, O2(.-), and OH radicals via type-II- 
      and type-I-dependent reaction mechanism, which corroborated by its specific 
      quenchers. 2'-dGua degradation in photochemical and % tail DNA formation in cell 
      line using comet test advocated the genotoxic potential of OFLX. Photocytotoxic 
      assays (MTT and NRU) revealed the considerable decline in cell viability by OFLX. 
      OFLX triggered apoptosis, proved by cell cycle, Annexin V/PI double staining 
      along with acridine orange (AO)/ethidium bromide (EB), and Hoechst staining as 
      well as caspase-3 activity by colorimetric assay. OFLX induced lysosomal 
      disruption and mitochondrial membrane destabilization confirmed through 
      fluorescence staining with AO/JC-1. OFLX significantly upregulated the expression 
      of p21 and bax genes. In conclusion, the study revealed that photosensitized OFLX 
      induced apoptosis via ROS-mediated DNA damage, destabilization of lysosomal and 
      mitochondrial membrane, and upregulation of p21, bax, and caspase-3 genes.
FAU - Dwivedi, A
AU  - Dwivedi A
AD  - Division of Photobiology, CSIR-Indian Institute of Toxicology Research , Lucknow 
      , India.
FAU - Mujtaba, S F
AU  - Mujtaba SF
FAU - Yadav, N
AU  - Yadav N
FAU - Kushwaha, H N
AU  - Kushwaha HN
FAU - Amar, S K
AU  - Amar SK
FAU - Singh, S K
AU  - Singh SK
FAU - Pant, M C
AU  - Pant MC
FAU - Ray, R S
AU  - Ray RS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140107
PL  - England
TA  - Free Radic Res
JT  - Free radical research
JID - 9423872
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - A4P49JAZ9H (Ofloxacin)
SB  - IM
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Apoptosis/*drug effects/*radiation effects
MH  - Cell Cycle/drug effects/radiation effects
MH  - Cell Survival/drug effects/radiation effects
MH  - Cells, Cultured
MH  - DNA Damage
MH  - Humans
MH  - Keratinocytes/drug effects/pathology/radiation effects
MH  - Ofloxacin/*toxicity
MH  - Photochemical Processes
MH  - Reactive Oxygen Species/metabolism
MH  - *Sunlight
MH  - *Ultraviolet Rays
EDAT- 2013/11/30 06:00
MHDA- 2014/12/15 06:00
CRDT- 2013/11/30 06:00
PHST- 2013/11/30 06:00 [entrez]
PHST- 2013/11/30 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.3109/10715762.2013.869324 [doi]
PST - ppublish
SO  - Free Radic Res. 2014 Mar;48(3):333-46. doi: 10.3109/10715762.2013.869324. Epub 
      2014 Jan 7.