title: 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model.
abstract: The custom use of radiotherapy was found to participate in the development of chronic unhealed wounds. In general, exposure to gamma radiation stimulates the production of reactive oxygen species (ROS) that eventually leads to damaging effect. Conversely, overexpression of a nuclear poly (ADP-ribose) polymerase enzyme (PARP) after oxidative insult extremely brings about cellular injury due to excessive consumption of NAD and ATP. Here, we dedicated our study to investigate the role of 3-aminobenzamide (3-AB), a PARP inhibitor, on pregamma irradiated wounds. Two full-thickness (6 mm diameter) wounds were created on the dorsum of Swiss albino mouse. The progression of wound contraction was monitored by capturing daily photo images. Exposure to gamma radiation (6Gy) exacerbated the normal healing of excisional wounds. Remarkably, topical application of 3-AB cream (50 µM) revealed a marked acceleration in the rate of wound contraction. Likewise, PARP inhibition ameliorated the unbalanced oxidative/nitrosative status of granulated skin tissues. Such effect was significantly revealed by the correction of the reduced antioxidant capacity and the enhanced lipid peroxidation, hydrogen peroxide, and myeloperoxidase contents. Moreover, application of 3-AB modified the cutaneous nitrite content throughout healing process. Conversely, the expressions of pro-inflammatory cytokines were down-regulated by PARP inhibition. The mitochondrial ATP content showed a lower consumption rate on 3-AB-treated wound bed as well. In parallel, the mRNA expressions of Sirt-1 and acyl-COA oxidase-2 (ACOX-2) were up-regulated; whom functions control the mitochondrial ATP synthesis and lipid metabolism. The current data suggested that inhibition of PARP-1 enzyme may accelerate the delayed wound healing in whole body gamma irradiated mice by early modifying the oxidative stress as well as the inflammatory response.
authors.affiliation: Cyclotron Project, Nuclear Physics Department, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, Egypt.|Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
authors.forename: Tarek
authors.initials: T
authors.lastname: El-Hamoly
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ezzeddin S
authors.initials: ES
authors.lastname: El-Denshary
authors.affiliation: Nuclear Physics Department, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, Egypt.
authors.forename: Shokry Mohamed
authors.initials: SM
authors.lastname: Saad
authors.affiliation: Drug Radiation Research Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
authors.forename: Mona A
authors.initials: MA
authors.lastname: El-Ghazaly
mesh_terms: D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005720:Gamma Rays / Q000009:adverse effects; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D012313:RNA / Q000008:administration & dosage; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001549:Benzamides; D016207:Cytokines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012313:RNA; C025160:3-aminobenzamide
keywords: ATP; Cytokines; Oxidative Stress; PARP; Radiotherapy; Wound