Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats

Rui Liu, Kazi Mokim Ahmed, Danupon Nantajit, Frank S. Rosenthal, Chun Xun Hai, Jian-Jian Li

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pulmonary fibrosis (PF) is a major side effect of radiotherapy and chemotherapy. Recent clinical trials, unfortunately, have failed to identify any therapeutic agent which has the potential to reduce the consequences of this devastating condition. Reactive oxygen species and tissue remodeling regulators, such as metalloproteinases (MMPs) and their inhibitors (TIMPs), are thought to be involved in the development of PF. We investigated these factors to determine the protective effects of antioxidant α-lipoic acid (LA) against antineoplastic agent bleomycin (BLM)-induced oxidant lung toxicity in Sprague-Dawley rats. At different time intervals after BLM administration, pathological changes of the lung were analyzed with the measurement of total protein in bronchoalveolar lavage fluid (BALF), hydroxyproline (HYP) content and the level of three oxidative stress markers, i.e. malondialdehyde (MDA), the GSH/GSSG ratio, and total antioxidative capability (T-AOC). Also, the expression changes of MMP-1 and TIMP-1 were measured. At day 14 or 28 after BLM administration, protein content in BALF, and HYP, MDA and T-AOC contents of the lung increased significantly with a decreased GSH/GSSG ratio, implicating an increased efflux of GSSG from the lung and consumption of GSH. In contrast, treatment with LA protected BLM-induced pulmonary injury by suppressing oxidative stress with the reduction of MDA, and the enhancement of the GSH/GSSG ratio and T-AOC. The BLM-stimulated symptoms of PF were relieved with significant reduction of HYP and total proteins in LA-treated rats. LA also ameliorated the MMP-1/TIMP-1 ratio. These results suggest that LA inhibits BLM-induced lung toxicity associated with oxidative damage. Therefore, antioxidant LA has a potential therapeutic effect in the prevention and alleviation of PF.

Original languageEnglish (US)
Pages (from-to)865-873
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume19
Issue number6
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Thioctic Acid
Pulmonary Fibrosis
Bleomycin
Therapeutic Uses
Glutathione Disulfide
Hydroxyproline
Lung
Malondialdehyde
Tissue Inhibitor of Metalloproteinase-1
Bronchoalveolar Lavage Fluid
Matrix Metalloproteinases
Oxidative Stress
Antioxidants
Proteins
Matrix Metalloproteinase Inhibitors
Lung Injury
Metalloproteases
Oxidants
Antineoplastic Agents
Sprague Dawley Rats

Keywords

  • α-lipoic acid
  • Bleomycin
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Genetics

Cite this

Liu, R., Ahmed, K. M., Nantajit, D., Rosenthal, F. S., Hai, C. X., & Li, J-J. (2007). Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats. International Journal of Molecular Medicine, 19(6), 865-873.

Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats. / Liu, Rui; Ahmed, Kazi Mokim; Nantajit, Danupon; Rosenthal, Frank S.; Hai, Chun Xun; Li, Jian-Jian.

In: International Journal of Molecular Medicine, Vol. 19, No. 6, 06.2007, p. 865-873.

Research output: Contribution to journalArticle

Liu, R, Ahmed, KM, Nantajit, D, Rosenthal, FS, Hai, CX & Li, J-J 2007, 'Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats', International Journal of Molecular Medicine, vol. 19, no. 6, pp. 865-873.
Liu, Rui ; Ahmed, Kazi Mokim ; Nantajit, Danupon ; Rosenthal, Frank S. ; Hai, Chun Xun ; Li, Jian-Jian. / Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats. In: International Journal of Molecular Medicine. 2007 ; Vol. 19, No. 6. pp. 865-873.
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