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SRT1720, A SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice

Author(s): Takashi Kondo | Masakiyo Sasahara | Kazuyuki Tobe | Hirofumi Ogawa | Ryuji Hayashi | Shingo Imanishi | Kensuke Suzuki | Tomomi Ichikawa

Journal: Advances in Molecular Imaging
ISSN 2161-6728

Volume: 03;
Issue: 02;
Start page: 157;
Date: 2012;
Original page

Keywords: Interstitial Lung Diseases (ILDs) | Lung Injury; SIRT1 | Bleomycin; X-Ray Irradiation; Oxidative Stress

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.

Tango Jona
Tangokurs Rapperswil-Jona

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