An experimental study of rabbit conjunctival epithelial toxicity using co-treatment with mitomycin-C and a histone deacetylase inhibitor.
This study was conducted to evaluate cytotoxicity due to co-treatment with low-dose Mitomycin-C (MMC) and the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA) for glaucoma filtration surgery. In this study, the effect of co-treatment with MMC and SAHA to induce apoptosis in cultured conjunctival epithelial cells (CEs) in rabbit was investigated. The cytotoxic potential following co-treatment with MMC and SAHA in CEs via assay for reactive oxygen species (ROS) and lactate dehydrogenase (LDH) was also examined. Co-treatment with MMC and SAHA did not induce apoptosis in CEs. In addition, co-treatment with MMC and SAHA caused no significant alteration of ROS and LDH levels in CEs. This study therefore shows that low-dose MMC could still be used as an antimetabolite in co-treatment with SAHA to effectively inhibit fibrosis of Tenon's capsule fibroblasts (TCFs) following glaucoma filtration surgery, while minimizing cytotoxicity in CEs.
Kim
Tae-Hyun
TH
Department Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, Busan, 602-714, Korea.
Oh
Hyun Cheol
HC
Yoo
Young Hyun
YH
Rho
Jee Hyun
JH
Park
Woo Chan
WC
Ahn
Hee Bae
HB
Jeung
Woo Jin
WJ
Rho
Sae Heun
SH
D000477:Alkylating Agents / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis / Q000517:prevention & control; D018463:Filtering Surgery / Q000379:methods; D005901:Glaucoma / Q000601:surgery; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D058475:Tenon Capsule / Q000187:drug effects / Q000473:pathology; D000077337:Vorinostat
D000477:Alkylating Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; D016685:Mitomycin; D000077337:Vorinostat; D007770:L-Lactate Dehydrogenase