Giuseppe
Emeritus
Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model (BMC, abstract, edited)
[Source Full Free PDF Document: LINK. EDITED.]
BMC Pulmonary Medicine - Research article Open Access
Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model
Takayoshi Fujibayashi?1, Naozumi Hashimoto?2, Mayumi Jijiwa3, Yoshinori Hasegawa2, Toshihisa Kojima*1 and Naoki Ishiguro1
Address: 1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan and 3Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Email: Takayoshi Fujibayashi - takafuji@med.nagoya-u.ac.jp; Naozumi Hashimoto - hashinao@med.nagoya-u.ac.jp; Mayumi Jijiwa - j2w@med.nagoya-u.ac.jp; Yoshinori Hasegawa - yhasega@med.nagoya-u.ac.jp; Toshihisa Kojima* - toshik@med.nagoya- u.ac.jp; Naoki Ishiguro - n-ishi@med.nagoya-u.ac.jp
* Corresponding author
?Equal contributors
Published: 16 September 2009
BMC Pulmonary Medicine 2009, 9:45 doi:10.1186/1471-2466-9-45
Received: 30 December 2008
Accepted: 16 September 2009
This article is available from: LINK
? 2009 Fujibayashi et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (LINK), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background:
To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against druginduced lung injury/fibrosis in vivo.
Methods:
We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.
Results:
We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle- treated mice.
Conclusion:
GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.
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[Source Full Free PDF Document: LINK. EDITED.]
BMC Pulmonary Medicine - Research article Open Access
Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model
Takayoshi Fujibayashi?1, Naozumi Hashimoto?2, Mayumi Jijiwa3, Yoshinori Hasegawa2, Toshihisa Kojima*1 and Naoki Ishiguro1
Address: 1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan and 3Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Email: Takayoshi Fujibayashi - takafuji@med.nagoya-u.ac.jp; Naozumi Hashimoto - hashinao@med.nagoya-u.ac.jp; Mayumi Jijiwa - j2w@med.nagoya-u.ac.jp; Yoshinori Hasegawa - yhasega@med.nagoya-u.ac.jp; Toshihisa Kojima* - toshik@med.nagoya- u.ac.jp; Naoki Ishiguro - n-ishi@med.nagoya-u.ac.jp
* Corresponding author
?Equal contributors
Published: 16 September 2009
BMC Pulmonary Medicine 2009, 9:45 doi:10.1186/1471-2466-9-45
Received: 30 December 2008
Accepted: 16 September 2009
This article is available from: LINK
? 2009 Fujibayashi et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (LINK), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background:
To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against druginduced lung injury/fibrosis in vivo.
Methods:
We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.
Results:
We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle- treated mice.
Conclusion:
GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.
-
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