title: Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model.
abstract: Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p < 0.01). NO-NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fukunaga
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa-Ishizawa
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Horinouchi
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Eriko
authors.initials: E
authors.lastname: Sairyo
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Pharmacy, Tokushima University Hospital.|Department of Clinical Pharmacy, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.affiliation: Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Plastic and Reconstructive Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hashimoto
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D006085:Graft Survival / Q000187:drug effects*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000188:drug therapy* / Q000473:pathology; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009603:Nitroso Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species; D013524:Surgical Flaps / Q000098:blood supply / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000975:Antioxidants; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; C539379:nitrosonifedipine; D009543:Nifedipine