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