Diterpene ginkgolides meglumine injection protects against paraquat-induced lung injury and pulmonary fibrosis in rats

Biomed Pharmacother. 2018 Mar:99:746-754. doi: 10.1016/j.biopha.2018.01.135. Epub 2018 Feb 20.

Abstract

In this study, we aimed to investigate the effects of diterpene ginkgolides meglumine injection (DGMI) on paraquat (PQ)-induced lung injury and pulmonary fibrosis in rats. Male SD rats were challenged by PQ (20?mg/kg, i.p.) with or without either DGMI (1.25, 2.5, 5?mg/kg, i.p.) or Edaravone (EDA, 6?mg/kg, i.p.) posttreatment 2?h after PQ administration. Lung tissues were removed for biochemical analyses and pathological examinations on day 1, day 3, day 7, day 14 and day 21. Results showed that the administration of DGMI significantly increased the survival of PQ-challenged rats. At the same time, DGMI reversed the increase of Malondialdehyde (MDA) level and the decrease of Super Oxide Dismutase (SOD) level in lung tissues. Moreover, lung to body weight ratio, Interleukin-1beta (IL-1?), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-?) levels in lung tissues were reduced compared with the model group. H&E and Masson staining revealed that DGMI (5?mg/kg) alleviated histological injury and pulmonary fibrosis, and EDA (6?mg/kg) exerted approximate effects. Immunohistochemistry staining presented that the benefit effects of DGMI were associated with its ability to activate Akt-Nrf-2 pathway. In conclusion, these results suggest that DGMI possesses potential role in future therapies for PQ-induced lung injury and pulmonary fibrosis.

Keywords: Diterpene ginkgolides meglumine injection; Lung injury; Paraquat; Pulmonary fibrosis.

MeSH terms

  • Acute Lung Injury
  • Animals
  • Antipyrine / analogs & derivatives
  • Antipyrine / pharmacology
  • Dose-Response Relationship, Drug
  • Edaravone
  • Ginkgolides / administration & dosage
  • Ginkgolides / pharmacology*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Meglumine / administration & dosage
  • Meglumine / pharmacology*
  • Pulmonary Edema / prevention & control*
  • Pulmonary Fibrosis / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Ginkgolides
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Meglumine
  • Superoxide Dismutase
  • Edaravone
  • Antipyrine

Supplementary concepts

  • Paraquat lung