Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation

Vasanthi R. Sunil, Kinal N. Vayas, Jessica A. Cervelli, Rama Malaviya, Le Roy Hall, Christopher B. Massa, Andrew J. Gow, Jeffrey D. Laskin, Debra L. Laskin

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (150-174g; 8-10weeks) to NM (0.125mg/kg, i.t.) resulted in severe histopathological changes in the lung within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2+ and MMP-9+), and anti-inflammatory/wound repair (CD163+ and Gal-3+) macrophages. Treatment of rats with pentoxifylline (46.7mg/kg, i.p.) daily for 3d beginning 15min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163+ and Gal-3+ macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalExperimental and Molecular Pathology
Volume97
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Mechlorethamine
Pentoxifylline
Oxidative stress
Acute Lung Injury
Oxidative Stress
Macrophages
Lung Injury
Inflammation
Pneumonia
Heme Oxygenase-1
Bronchoalveolar Lavage
Matrix Metalloproteinases
Lung
Rats
Repair
Tumor Necrosis Factor-alpha
Lipocalins
Irritants
Poisons
Alkylating Agents

Keywords

  • Lung injury
  • Macrophages
  • Mustards
  • Oxidative stress
  • Pentoxifylline
  • Vesicants

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Sunil, V. R., Vayas, K. N., Cervelli, J. A., Malaviya, R., Hall, L. R., Massa, C. B., ... Laskin, D. L. (2014). Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. Experimental and Molecular Pathology, 97(1), 89-98. https://doi.org/10.1016/j.yexmp.2014.05.009

Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. / Sunil, Vasanthi R.; Vayas, Kinal N.; Cervelli, Jessica A.; Malaviya, Rama; Hall, Le Roy; Massa, Christopher B.; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

In: Experimental and Molecular Pathology, Vol. 97, No. 1, 2014, p. 89-98.

Research output: Contribution to journalArticle

Sunil, VR, Vayas, KN, Cervelli, JA, Malaviya, R, Hall, LR, Massa, CB, Gow, AJ, Laskin, JD & Laskin, DL 2014, 'Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation', Experimental and Molecular Pathology, vol. 97, no. 1, pp. 89-98. https://doi.org/10.1016/j.yexmp.2014.05.009
Sunil, Vasanthi R. ; Vayas, Kinal N. ; Cervelli, Jessica A. ; Malaviya, Rama ; Hall, Le Roy ; Massa, Christopher B. ; Gow, Andrew J. ; Laskin, Jeffrey D. ; Laskin, Debra L. / Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. In: Experimental and Molecular Pathology. 2014 ; Vol. 97, No. 1. pp. 89-98.
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