Oleanolic acid improves pulmonary morphofunctional parameters in experimental sepsis by modulating oxidative and apoptotic processes

Respir Physiol Neurobiol. 2013 Dec 1;189(3):484-90. doi: 10.1016/j.resp.2013.08.019. Epub 2013 Sep 4.

Abstract

We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups. Sepsis was induced by cecal ligation and puncture, while the control group underwent sham surgery. 1h after surgery, all animals were further randomized to receive saline (SAL), OA and dexamethasone (DEXA) intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which were associated with fewer lung neutrophils and less cell apoptosis in lung, liver, and kidney than SAL. However, only animals in the DEXA group had lower levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar lavage fluid than SAL animals. Conversely, OA was associated with lower inducible nitric oxide synthase expression and higher superoxide dismutase than DEXA. In the experimental sepsis model employed herein, OA and DEXA reduced lung damage and distal organ apoptosis through distinct anti-inflammatory mechanisms.

Keywords: Chemokine; Cytokines; Dexamethasone; Histology; Lung mechanics; Oxidative stress.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Catalase / genetics
  • Catalase / metabolism
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Lung / drug effects
  • Lung / pathology*
  • Lung / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oleanolic Acid / therapeutic use*
  • Oxidative Stress / drug effects*
  • Sepsis / complications
  • Sepsis / drug therapy
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Oleanolic Acid
  • Dexamethasone
  • Catalase
  • Glutathione Peroxidase
  • Nitric Oxide Synthase Type II
  • Superoxide Dismutase