In-vivo antioxidant and anti-inflammatory activity of rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists in animal model of bronchial asthma

J Pharm Pharmacol. 2015 Oct;67(10):1421-30. doi: 10.1111/jphp.12445. Epub 2015 Jun 23.

Abstract

Objectives: Peroxisome proliferator activated receptor-gamma (PPAR-γ) has been shown to play an important role in the control of immunological and inflammatory responses. This study aims at investigating the potential role of rosiglitazone, a strong PPAR-γ agonist in a murine model of bronchial asthma.

Methods: Adult male guinea pigs were administered ovalbumin 100 mg/kg subcutaneous (SC) and 100 mg/kg intraperitoneal (IP). Treatment with rosiglitazone [5 mg/kg/day, per oral (PO)] was assessed for 21 days. On day 21, the animals were challenged with the same dose of ovalbumin. The forced expiratory volume in 1 s (FEV1 ) to forced vital capacity (FVC), FEV1 /FVC, was measured using a spirometer to diagnosis lung obstruction. Serum levels of interleukin-5 (IL-5) and immunoglobulin E (IgE) were assessed. The activity of superoxide dismutase (SOD) and catalase and the level of reduced glutathione (GSH) were determined in lung tissue homogenates.

Key findings: Our results demonstrated that treatment with rosiglitazone resulted in a statistically significant improvement in lung function and histopathological features. Significant decrease in the serum levels of IL-5 and IgE were observed. The activity of SOD and catalase as well as the GSH level were significantly increased in the lung tissues of treated animals compared with untreated asthmatic animals. Serum IgE concentrations and IL-5 levels were directly correlated to each other and inversely correlated to the SOD, GSH and catalase levels in the all studied guinea pigs.

Conclusions: Our results provide evidence that the PPAR-γ agonist rosiglitazone may have potential in the development of therapies for bronchial asthma.

Keywords: bronchial asthma; immunoglobulin E; interleukin-5; peroxisome proliferator-activated receptor-gamma; rosiglitazone.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Catalase / metabolism
  • Disease Models, Animal
  • Glutathione / metabolism
  • Guinea Pigs
  • Immunoglobulin E / blood
  • Interleukin-5 / blood
  • Male
  • Ovalbumin / immunology
  • PPAR gamma / agonists*
  • Rosiglitazone
  • Superoxide Dismutase / metabolism
  • Thiazolidinediones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Interleukin-5
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Immunoglobulin E
  • Ovalbumin
  • Catalase
  • Superoxide Dismutase
  • Glutathione