Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Wound healing is a complex process involving various cellular and humoral factors. We set out to investigate the role of poly(ADP-ribosyl)ation in wound healing. We found that topically applied PARP inhibitors 3-aminobenzamide and PJ-34 accelerated wound closure in a mouse model of excision wounding. Moreover, wounds also closed faster in PARP-1 knockout mice as compared to wild type littermates. Immunofluorescent staining for poly(ADP-ribose) indicated increased PAR synthesis in scattered cells of the wound bed. Expression of IL-6, TNF-Ü, inducible nitric oxide synthase and matrix metalloproteinase-9 was lower in the wounds of PARP-1 knockout mice as compared to control, whereas expression of IL-1Ý, cyclooxygenase-2, TIMP-1 and -2 were only slightly affected. The level of nitrotyrosine (a marker of nitrating stress) was also lower in the wounds of PARP-1 knockout animals as compared to controls. In vitro scratch assays revealed significantly faster migration of keratinocytes treated with 3-aminobenzamide (3-AB) or PJ34 as compared to control cells. These data suggest that poly (ADP-ribosyl)ation by PARP-1 slows down the wound healing process by increasing the production of inflammatory mediators and nitrating stress and by slowing the migration of keratinocytes. The second part of the study was related to the impact of ionizing on wound healing

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