The Evaluation of Human Tenon's Fibroblasts and Endothelial Cell Responses to Antifibrotics Alone and in Combination with α-Tocopherol


ENGIN K. N., Erdem-Kuruca S., Akgun-Dar K., Cetin B., Karadenizli S., Gurel E., ...Daha Fazla

CURRENT EYE RESEARCH, sa.1, ss.19-29, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/02713683.2014.909496
  • Dergi Adı: CURRENT EYE RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.19-29
  • Anahtar Kelimeler: alpha-tocopherol, 5-fluorouracil, antifibrotic, apoptosis, endothelium, glaucoma surgery, Tenon's fibroblast, mitomycin, GLAUCOMA FILTRATION SURGERY, MITOMYCIN-C, IN-VITRO, VITAMIN-E, INHIBITS PROLIFERATION, CORNEAL ENDOTHELIUM, CAPSULE FIBROBLASTS, EXPERIMENTAL-MODEL, FILTERING SURGERY, CYCLOSPORINE-A
  • İstanbul Üniversitesi Adresli: Evet

Özet

Purpose: We aimed to evaluate the influence of current antifibrotic agents as well as the possible results obtained by combining these agents. This study included alpha-tocopherol, a strong antifibrotic and an efficient neuromediator of pathways used by other agents. Materials and Methods: Mitochondrial Bcl-2, Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect patterns, mitosis and cellular reactions due to alpha-tocopherol alone or combined with paclitaxel, mitomycin C and 5-flurouracil (5-FU), was studied in series obtained from human endothelial and primary Tenon's fibroblast cell cultures. Results: The strongest apoptotic effect in both cell groups belonged to paclitaxel, followed by mitomycin C, and despite the overall suppressive effect of the alpha-tocopherol combination, mitomycin C increased its efficiency on the endothelial cells. The apoptosis/necrosis ratio was highest in alpha-tocopherol and lowest in paclitaxel, with alpha-tocopherol generally decreasing necrosis. Bax was observed at a high level with mitomycin C. Cytotoxicity was the highest with paclitaxel, and the caspase-3 reaction was markedly higher with mitomycin C in both cell types. In the alpha-tocopherol and 5-FU slides, mitosis and a layered formation were observed. The addition of alpha-tocopherol reduced the cytotoxicity of all antifibrotic agents in both cell series by decreasing the cell numbers, leading to necrosis. Conclusions: Alone or in combination, the use of alpha-tocopherol and 5-FU is safer than other agents. By suppressing the cytotoxic effects of other antifibrotic agents, alpha-tocopherol is a promising drug for improving the effects of antifibrotics in many aspects of medicine. In addition, it has the potential to play a role beyond its antioxidant and antifibrotic activity in ocular surgery.