title: Evaluation of the toxicity of triamcinolone acetonide and dexamethasone sodium phosphate on human lens epithelial cells (HLE B-3).
abstract: OBJECTIVE
  The purpose of this study was to compare the in vitro effects of triamcinolone acetonide (TA) and dexamethasone sodium phosphate (DEX) on human lens epithelial cells (HLE B-3).
  
  
  METHODS
  HLE B-3 cells were exposed for 24 h to commercially available TA (c-TA) and dimethylsulfoxide-solubilized TA (s-TA). The cells were treated with 1,000 (clinical dose), 750, 500, 200, and 100 μg/mL concentrations of c-TA, s-TA, and supernatant for 24 h. The cells were also treated with DEX at 2, 1, 0.5, 0.2, 0.1 (clinical dose), and 0.05 mg/mL. Cell viability, caspase-3/7 activity, and DNA fragmentation analyses were performed.
  
  
  RESULTS
  The mean cell viabilities of HLE B-3 after exposure to c-TA at 1,000, 750, 500, 200, and 100 μg/mL were significantly reduced compared with control untreated cells. The s-TA also significantly reduced cell viability at 1,000, 750, and 500 μg/mL compared with dimethylsulfoxide control. The supernatant did not reduce cell viability. Caspase-3/7 activity significantly increased after treatment with c-TA and s-TA. DNA laddering revealed bands at 200 bp intervals with both c-TA at≥100 μg/mL and s-TA at ≥500 μg/mL. The cell viabilities of HLE B-3 after 24 h exposure to DEX were significantly reduced at 2 and 1 mg/mL but not at lower concentrations tested. Caspase-3/7 activities in HLE B-3 cells were not increased significantly after treatment with DEX at any dose tested. DNA laddering did not reveal any band at any dose tested.
  
  
  CONCLUSIONS
  This study showed that TA at its clinical dose (1,000 μg/mL) in both commercial preparation and solubilized forms decrease HLE B-3 cell viability through an apoptotic pathway. DEX at its clinical dose (0.1 mg/mL) does not decrease cell viability or cause any increase of caspase-3/7 activity. This study suggests that for long-term sustained-release devices, DEX may be less damaging to human lens cells than TA.
authors.affiliation: Gavin Herbert Eye Institute Department of Ophthalmology, School of Medicine, University of California at Irvine, Irvine, California 92697, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Sharma
authors.forename: Ashkan
authors.initials: A
authors.lastname: Pirouzmanesh
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Patil
authors.forename: M F
authors.initials: MF
authors.lastname: Estrago-Franco
authors.forename: Leandro Cabral
authors.initials: LC
authors.lastname: Zacharias
authors.forename: Aslan
authors.initials: A
authors.lastname: Pirouzmanesh
authors.forename: Usha P
authors.initials: UP
authors.lastname: Andley
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000633:toxicity; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects*; D005938:Glucocorticoids / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects*; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D012995:Solubility; D014222:Triamcinolone Acetonide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D014677:Pharmaceutical Vehicles; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D014222:Triamcinolone Acetonide; D004121:Dimethyl Sulfoxide