Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia-reperfusion injury.
Ischaemia-reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non-blanchable erythema. However, there is no evidence-based treatment for early-stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31(+) vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress-associated DNA-damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF-E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68(+) macrophages and the level of transforming growth factor-beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress-induced tissue damage. Topical steroids might not be recommended for the treatment of acute-phase decubitus ulcers.
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Akihiko
A
Uchiyama
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Kazuya
K
Yamada
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Buddhini
B
Perera
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Sachiko
S
Ogino
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Yoko
Y
Yokoyama
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Yuko
Y
Takeuchi
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Osamu
O
Ishikawa
Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Sei-Ichiro
S
Motegi
D000279:Administration, Cutaneous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001623:Betamethasone / Q000009:adverse effects / Q000031:analogs & derivatives*; D000075203:Contraindications, Drug; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D003668:Pressure Ulcer / Q000188:drug therapy* / Q000209:etiology; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D012867:Skin / Q000098:blood supply
D016207:Cytokines; C000612965:betamethasone butyrate propionate; D001623:Betamethasone
decubitus ulcers; macrophage; oxidative stress; reactive oxygen species; topical steroid