Abstract
Purpose. To evaluate the dose effect of vitamin K3 on wound healing mechanisms. Methods. Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [3H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L, group 4/vitamin K3 2 mg/L, group 5/vitamin K3 4 mg/L, and group 6/vitamin K3 6 mg/L. Each experiment was carried out in triplicate and 4 times. Results. There were no differences among groups at the initial time. In vitro wound repair was slower in groups 4, 5, and 6. There were no differences between control and ethanol groups and between control and vitamin K3 1 mg/L groups. Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too. In groups 5 and 6, cellular toxicity was presented. Conclusions. Vitamin K3 is able to inhibit fibroblast proliferation. Vitamin K3 2 mg/L or higher doses inhibit wound healing repair, exhibiting cellular toxicity at 4 and 6 mg/L.
Highlights
Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too
[29,30,31], disintegrins [32], siRNA-PKCα [33]. . . are some of the useful drugs that have been used in the treatment of conditions such as proliferative vitreoretinopathy, bleb scarring after trabeculectomy, and other disorders with cell proliferation
Dulbecco’s Modified Eagles Medium (DMEM), phosphate buffer saline (PBS), fetal calf serum (FCS), and antibiotics-antifungals were purchased from GIBCO (Madison, WI). [methyl-3H]thymidine was purchased from Amershm Iberica (Madrid, Spain). 2-Methyl 1,4-Naphthoquinone (Menadione) (98%) was obtained from Sigma
Summary
Antimetabolites and other fibroblast inhibitor drugs have been shown to enhance the success rate of filtering surgery depending on the dose, they can lead to severe complications and may result in the failure of the surgery.Corticosteroids [1,2,3,4,5,6] antiproliferative agents (5-fluorouracil and other fluoropyrimidines, taxol, doxorubicin, mycophenolate mofetil. . ., alone or in combination or with different delivery systems) [3,4,5,6,7,8,9,10,11,12], systemic, periocular, intraocular steroidal, and nonsteroidal anti-inflammatory agents [5, 13,14,15,16], colchicine [8], daunomycin [8], tissue plasminogen activator [17], heparin [12, 18,19,20], interferon-gamma [21, 22], calcium channel blockers [23], prolyl and lysyl hydroxylase inhibitors [19, 24,25,26], retinoic acid [27, 28], alpha-tocopherol [29,30,31], disintegrins [32], siRNA-PKCα [33]. . . are some of the useful drugs that have been used in the treatment of conditions such as proliferative vitreoretinopathy, bleb scarring after trabeculectomy, and other disorders with cell proliferation (progressive conjunctival or extraocular cicatrization).Vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone) has been used as antihemorrhagic agent. Its ability to inhibit proliferation of tumor cells has already been reported; its activity has been demonstrated in human tumor stem cell and it is used in clinical trial for advanced malignancies acting in different pathways and has been related to other oxidative stress processes at the eye level as cataract formation. Liu et al reported that this drug could inhibit proliferation of rabbit conjunctive cells [41]. The Scientific World Journal (a) 24 hours (b) 48 hours (c) (d). The aim of this study was to evaluate and to compare the antiproliferative properties of vitamin K3 in cultured human fibroblasts Liu et al reported that this drug could inhibit proliferation of rabbit conjunctive cells [41]. 0 hours 18 hours
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