TITLE:
SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice
AUTHORS:
Shingo Imanishi, Ryuji Hayashi, Tomomi Ichikawa, Kensuke Suzuki, Masakiyo Sasahara, Takashi Kondo, Hirofumi Ogawa, Kazuyuki Tobe
KEYWORDS:
Interstitial Lung Diseases (ILDs), Lung Injury; SIRT1, Bleomycin; X-Ray Irradiation; Oxidative Stress
JOURNAL NAME:
Food and Nutrition Sciences,
Vol.3 No.2,
February
27,
2012
ABSTRACT: 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.