Nicotine enhances skin necrosis and expression of inflammatory mediators in a rat pressure ulcer model

S. Tsutakawa, D. Kobayashi, M. Kusama, Takahiro Moriya, N. Nakahata

研究成果: Article査読

18 被引用数 (Scopus)


Background Many bedridden patients develop pressure ulcers, not only in hospital but also at home. Clinical studies have indicated cigarette smoking to be a risk factor for pressure ulcers. However, the contribution of nicotine to pressure ulcer formation has not been identified. Objectives We aimed to clarify the effect of nicotine on pressure ulcer formation, and its mechanism. Methods Ischaemia-reperfusion (I/R) was performed in rat dorsal skin to induce pressure ulcers. The extent of the resulting necrotic area was determined. To clarify the mechanism of the effect of nicotine, mRNA levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS) and protein expression of COX-2 and iNOS in the necrotic area were investigated by real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. Furthermore, the effects of the COX-2 inhibitor NS-398 and the iNOS inhibitor aminoguanidine on necrosis were examined. Results Skin necrosis in the I/R-treated area was significantly increased by intraperitoneal administration of nicotine (0·175 mg kg-1 daily). Repeated nicotine administration had little effect on systolic and diastolic blood pressure. I/R treatment increased mRNA levels of COX-2, IL-1β, IL-6 and iNOS, which were further augmented by nicotine in a dose-dependent manner. Correspondingly, nicotine (0·35 mg kg-1 daily) markedly enhanced the protein expression of COX-2 and iNOS. Moreover, NS-398 and aminoguanidine showed a tendency to abrogate the increase of I/R-induced skin necrosis caused by nicotine. Conclusions These results suggest that the increased risk of pressure ulcers due to cigarette smoking is mediated, in part, by nicotine. They also indicated that the effect of nicotine is not mediated by a change in blood pressure, but is elicited via an increase of inflammatory mediators in the I/R-treated skin.

ジャーナルBritish Journal of Dermatology
出版ステータスPublished - 2009 11月 1

ASJC Scopus subject areas

  • 皮膚病学


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