title: The evaluation of human tenon's fibroblasts and endothelial cell responses to antifibrotics alone and in combination with α-tocopherol.
abstract: OBJECTIVE
  We aimed to evaluate the influence of current antifibrotic agents as well as the possible results obtained by combining these agents. This study included α-tocopherol, a strong antifibrotic and an efficient neuromediator of pathways used by other agents.
  
  
  METHODS
  Mitochondrial Bcl-2, Bax, cytochrome c and cytoplasmic caspase-3 expression, as well as toxic effect patterns, mitosis and cellular reactions due to α-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 α-tocopherol combination, mitomycin C increased its efficiency on the endothelial cells. The apoptosis/necrosis ratio was highest in α-tocopherol and lowest in paclitaxel, with α-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 α-tocopherol and 5-FU slides, mitosis and a layered formation were observed. The addition of α-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 α-tocopherol and 5-FU is safer than other agents. By suppressing the cytotoxic effects of other antifibrotic agents, α-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.
authors.affiliation: Department of Ophthalmology, Ümraniye Education and Research Hospital , Istanbul , Turkey .
authors.forename: Kaya N
authors.initials: KN
authors.lastname: Engin
authors.forename: Serap
authors.initials: S
authors.lastname: Erdem-Kuruca
authors.forename: Kadriye
authors.initials: K
authors.lastname: Akgün-Dar
authors.forename: Beyza
authors.initials: B
authors.lastname: Çetin
authors.forename: Sabriye
authors.initials: S
authors.lastname: Karadenizli
authors.forename: Ebru
authors.initials: E
authors.lastname: Gürel
authors.forename: Bülent
authors.initials: B
authors.lastname: Yemisci
authors.forename: Sema
authors.initials: S
authors.lastname: Bilgiç
authors.forename: Mehmet
authors.initials: M
authors.lastname: Arslan
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D009336:Necrosis; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D058475:Tenon Capsule / Q000166:cytology*; D024502:alpha-Tocopherol / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D000975:Antioxidants; C494826:BAX protein, human; D004338:Drug Combinations; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016685:Mitomycin; D045304:Cytochromes c; D053148:Caspase 3; D024502:alpha-Tocopherol; D017239:Paclitaxel; D005472:Fluorouracil
keywords: 5-fluorouracil; Tenon's fibroblast; antifibrotic; apoptosis; endothelium; glaucoma surgery; mitomycin; α-tocopherol