Acute effects of glaucoma medications and benzalkonium chloride on pre-adipocyte proliferation and adipocyte cytotoxicity in vitro.
OBJECTIVE
To determine and compare the short-term, in vitro effect of prostaglandin analogues (PGAs), timolol, and benzalkonium chloride (BAK) on pre-adipocyte proliferation and adipocyte cytotoxicity.


METHODS
For the proliferation assay, human primary subcutaneous pre-adipocytes were incubated in the presence of either bimatoprost (0.015%, 0.03%, 0.06%) travoprost (0.002%, 0.004%, 0.008%), latanoprost (0.0025%, 0.005%, 0.010%), tafluprost (0.00075%, 0.0015%, 0.003%), timolol maleate (0.25%, 0.5%, 1.0%), BAK (0.005%, 0.010%, 0.015%, 0.020%, 0.040%), or control of BAK vehicle. After 72 h in culture, cell numbers were determined by fluorescent assay with CellTiter-Blue(®) reagent. For the cytotoxity assay, mature human adipocytes were cultured for 72 h with the same test compounds and controls. Cell numbers were again determined in the same manner through fluorescence.


RESULTS
In the proliferation assay, all four PGA medications failed to show a statistically significant difference from BAK vehicle alone (p = 0.065-0.751). Both timolol and BAK alone demonstrated near complete inhibition of pre-adipocyte proliferation at all concentrations tested (p < 0.01 for all). In the cytotoxicity assay, all four PGAs again exerted no significant effect when compared to control (p = 0.211-0.901). Timolol and BAK again displayed near complete toxicity of adipocytes at all concentrations (p < 0.01 for all).


CONCLUSIONS
All four PGAs had similar and negligible short-term effects on pre-adipocyte proliferation and adipocyte toxicity in vitro. Timolol and BAK had profound cytotoxic effects on mature adipocytes and antiproliferative effects on pre-adipocytes in vitro. Further testing is needed to determine whether similar effects are present in vivo.
University of Colorado Eye Center, Department of Ophthalmology, University of Colorado at Denver, Aurora, Colorado, USA.
Leonard K
LK
Seibold
David A
DA
Ammar
Malik Y
MY
Kahook
D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001548:Benzalkonium Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical