Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats

  • Authors:
    • Yang Bai
    • Yun Wang
    • Ming Liu
    • Yu‑Han Gu
    • Bin Jiang
    • Xu Wu
    • Huai‑Liang Wang
  • View Affiliations

  • Published online on: March 22, 2017     https://doi.org/10.3892/mmr.2017.6356
  • Pages: 3135-3142
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Abstract

The imbalance between oxidative stress and antioxidant defense is important in the pathogenesis of lung diseases. Nuclear factor erythroid‑2‑related factor 2 (Nrf2) is a key transcriptional factor that regulates the antioxidant response. The purpose of the present study was to investigate whether Nrf2‑mediated antioxidative defense is involved in methamphetamine (MA)‑induced lung injury in rats. Following establishment of chronic MA toxicity in rats, Doppler ultrasonic detection was used to measure the changes of physiological indexes, followed by hematoxylin and eosin staining, ELISA and western blot analysis. MA was demonstrated to increase the heart rate and peak blood flow velocity of pulmonary arterial valves and to decrease the survival rate of rats, and resulted in lung injury characterized by perivascular exudates, airspace edema, slight hemorrhage and inflammatory cell infiltration. MA significantly inhibited the expression of nuclear Nrf2 protein and its target genes (glutamate‑cysteine ligase catalytic subunit C and heme oxygenase‑1), and dose‑dependently reduced glutathione (GSH) levels and the ratio of GSH/oxidized glutathione, accompanied by increases in reactive oxygen species (ROS) levels in rat lungs. Linear regression analysis revealed that there was a positive correlation between lung ROS level and lung injury indexes. These findings suggested that chronic exposure to MA led to lung injury by suppression of Nrf2‑mediated antioxidative defense, suggesting that Nrf2 may be an important therapeutic target for MA‑induced chronic lung toxicity.
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May-2017
Volume 15 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Bai Y, Wang Y, Liu M, Gu YH, Jiang B, Wu X and Wang HL: Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats. Mol Med Rep 15: 3135-3142, 2017
APA
Bai, Y., Wang, Y., Liu, M., Gu, Y., Jiang, B., Wu, X., & Wang, H. (2017). Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats. Molecular Medicine Reports, 15, 3135-3142. https://doi.org/10.3892/mmr.2017.6356
MLA
Bai, Y., Wang, Y., Liu, M., Gu, Y., Jiang, B., Wu, X., Wang, H."Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats". Molecular Medicine Reports 15.5 (2017): 3135-3142.
Chicago
Bai, Y., Wang, Y., Liu, M., Gu, Y., Jiang, B., Wu, X., Wang, H."Suppression of nuclear factor erythroid‑2‑related factor 2‑mediated antioxidative defense in the lung injury induced by chronic exposure to methamphetamine in rats". Molecular Medicine Reports 15, no. 5 (2017): 3135-3142. https://doi.org/10.3892/mmr.2017.6356