%0 Journal Article
%T SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice
%A Shingo Imanishi
%A Ryuji Hayashi
%A Tomomi Ichikawa
%A Kensuke Suzuki
%A Masakiyo Sasahara
%A Takashi Kondo
%A Hirofumi Ogawa
%A Kazuyuki Tobe
%J Food and Nutrition Sciences
%P 157-163
%@ 2157-9458
%D 2012
%I Scientific Research Publishing
%R 10.4236/fns.2012.32024
%X Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer cells, caused by X-ray irradiation and an anti-Fas activating antibody, was promoted by SRT1720. These results indicate that SRT1720 not only aggravates bleomy- cin-induced ILD, but stimulates the apoptosis of physically and biologically stimulated A549 cells. While SIRT1 acti- vators are considered promising for the treatment of conditions such as diabetes mellitus, fatty liver, and chronic ob- structive pulmonary diseases, an excess of food containing SIRT1 activators may be harmful depending on the disease state, especially in the case of acute inflammation.
%K Interstitial Lung Diseases (ILDs)
%K Lung Injury
%K SIRT1
%K Bleomycin
%K X-Ray Irradiation
%K Oxidative Stress
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=17510