Korean J Intern Med.  2013 Jul;28(4):420-427. 10.3904/kjim.2013.28.4.420.

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

• Choi JS
• Jou SS
• Oh MH
• Kim YH
• Park MJ
• Gil HW
• Song HY
• Hong SY

• KMID: 1503779
• DOI: http://doi.org/10.3904/kjim.2013.28.4.420

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)-beta1 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-beta1 levels.

Keyword

Paraquat; Cyclophosphamide; Reactive oxygen species; X-ray microtomography

MeSH Terms

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