Wound healing efficacy of a class of antibacterial compounds
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Two compounds namely PKZ1800 and PKZ1822, showing antibacterial activity were assessed for cytotoxic effects on WI38 fetal lung fibroblast cells. PKZ1800 showed potential toxic effects at a concentration of 80μg/ml. Morphology of fibroblast-like appearing WI 38 cells changed to round up, detached cells beyond 80μg/ml. PKZ1822 showed an in vitro cytotoxic effect at a concentration much lower than that of PKZ1800. Subsequently an in vivo assay was performed to test the effect of PKZ1800 on wound healing in mice. Surgically produced full thickness wounds were treated with PKZ1800 over a 14-day period to analyse wound closure and toxic effects of the compound. General tracking of wound closure showed that by day 10 of the study, almost all the wounds were closed. However, wound closure in terms of area and circumference was found to be significantly better in the PKZ1800 treated wounds than that of the vehicle treated wound. No adverse toxic effects were seen in any of the mice during the entire study period. Relative organ weights of lung, liver and kidney showed no significant differences between the control and treated mice at any of the sacrifice time points indicating no potential toxicity in the mice. Histological analysis of PKZ1800 treated wound sections showed partial re-epithelialization of the skin by day 7 and complete re-epithelialization by day 14. Morphometric analysis of H&E images of day 7 wound sections indicated significantly better cellular infiltration in the dermis beneath the wound bed for the PKZ1800 treated wound. Collagen analysis of PKZ1800 treated wounds showed increased collagen density and collagen intensity compared to vehicle treated wounds. Evident hair follicle regeneration was also observed by day 14 of the study. Future directions include further image analyses to study folliculogenesis in detail and other cellular events occurring at each stage of wound healing in the experimental skin sections.