Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice

Inflamm Res. 2013 May;62(5):499-506. doi: 10.1007/s00011-013-0603-6. Epub 2013 Feb 23.

Abstract

Objective: Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods: Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 were detected by western blot.

Results: Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 caused by LPS.

Conclusion: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cytokines / metabolism
  • Gossypol / pharmacology
  • Gossypol / therapeutic use*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Peroxidase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Peroxidase
  • Mitogen-Activated Protein Kinases
  • Gossypol