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Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats

  • Organ Toxicity and Mechanisms
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Abstract

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) against carmustine (BCNU)-induced lung toxicity in rats. A total of 60 rats were randomly divided into four groups (15/group): control group in which the animals received 0.5 ml physiologic saline containing 10% ethanol (IP) weekly, MT-administered group in which rats received MT (30 μmol/kg, IP) weekly, BCNU-administered group in which rats received BCNU (5 mg/kg, IP) weekly and MT + BCNU group in which rats received weekly doses of BCNU (5 mg/kg, IP) followed 24 h later by MT (30 μmol/kg, IP). At the end of the experiment (after 6 weeks), lung histological changes, collagen staining, the activity of glutathione reductase (GR) and contents of reduced glutathione (GSH) and hydroxyproline (Hpr) in the lung as well as serum level of tumor necrosis factor-alpha (TNF-α) were evaluated. The obtained data revealed that BCNU induced pathological changes and markedly increased lung collagen and level of Hpr but decreased GSH content and GR activity and increased serum TNF-α compared to both control and MT-administered rats. Administration of MT + BCNU markedly improved histological features and decreased staining of collagen along with increased GR activity, GSH content but decreased level of Hpr in lung tissue as well as decreased serum level of TNF-α compared with BCNU-treated rats. Based on our results, it is possible to postulate that exogenous MT can act against BCNU-induced lung toxicity by a mechanism related, at least in part, to its ability to decrease oxidative stress and fibrosis.

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Acknowledgments

The present work was supported by grant (C. P. R. C. 175) from Research Center, College of Pharmacy, King Saud University, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia

    Gouda Kamel Helal

  2. Department of Histology, College of Medicine, Benha University, Benha, Egypt

    Omayma K. Helal

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  1. Gouda Kamel Helal
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Correspondence to Gouda Kamel Helal.

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Helal, G.K., Helal, O.K. Metallothionein attenuates carmustine-induced oxidative stress and protects against pulmonary fibrosis in rats. Arch Toxicol 83, 87–94 (2009). https://doi.org/10.1007/s00204-008-0325-7

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  • DOI: https://doi.org/10.1007/s00204-008-0325-7

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