Therapeutic effects of α-lipoic acid on bleomycin-induced pulmonary fibrosis in rats
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 regula...
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Published in | International journal of molecular medicine Vol. 19; no. 6; pp. 865 - 873 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Greece
D.A. Spandidos
01.06.2007
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 1107-3756 1791-244X |
DOI: | 10.3892/ijmm.19.6.865 |