The dose of cyclophosphamide for treating paraquat-induced rat lung injury

Korean J Intern Med. 2013 Jul;28(4):420-7. doi: 10.3904/kjim.2013.28.4.420. Epub 2013 Jul 1.

Abstract

Background/aims: Cyclophosphamide (CP) is a promising treatment for severe cases of paraquat (PQ) poisoning. We investigated the effective dose of CP for mitigating PQ-induced lung injury.

Methods: Adult male Sprague-Dawley rats were allocated into five groups: control, PQ (35 mg/kg, intraperitoneal injection), and PQ + CP (1.5, 15, or 30 mg/kg). The dimensions of lung lesions were determined using X-ray microtomography (micro-CT), and histological changes and cytokine levels were recorded.

Results: The micro-CT results showed that 15 mg/kg CP was more effective than 1.5 mg/kg CP for treating PQ-induced lung injury. At a dose of 1.5 mg/kg, CP alleviated the histological evidence of inflammation and altered superoxide dismutase activity. Using 15 mg/kg CP reduced the elevated catalase activity and serum transforming growth factor (TGF)-β1 level.

Conclusions: A CP dose of > 15 mg/kg is effective for reducing the severity of PQ-induced lung injury as determined by histological and micro-CT tissue examination, possibly by modulating antioxidant enzyme and TGF-β1 levels.

Keywords: Cyclophosphamide; Paraquat; Reactive oxygen species; X-ray microtomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury
  • Animals
  • Catalase / metabolism
  • Cyclophosphamide / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Immunosuppressive Agents / pharmacology*
  • Inflammation Mediators / metabolism
  • Lung / diagnostic imaging
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / chemically induced
  • Lung Injury / diagnosis
  • Lung Injury / drug therapy*
  • Lung Injury / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Paraquat*
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / diagnosis
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • X-Ray Microtomography

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Cyclophosphamide
  • Catalase
  • Superoxide Dismutase
  • Paraquat

Supplementary concepts

  • Paraquat lung