1.The dose of cyclophosphamide for treating paraquat-induced rat lung injury.
Jae Sung CHOI ; Sung Shick JOU ; Mee Hye OH ; Young Hee KIM ; Min Ju PARK ; Hyo Wook GIL ; Ho Yeon SONG ; Sae Yong HONG
The Korean Journal of Internal Medicine 2013;28(4):420-427
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.
Animals
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Catalase/metabolism
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Cyclophosphamide/*pharmacology
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Cytokines/metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Immunosuppressive Agents/*pharmacology
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Inflammation Mediators/metabolism
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Lung/*drug effects/metabolism/pathology/radiography
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Lung Injury/chemically induced/diagnosis/*drug therapy/metabolism
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Male
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Oxidative Stress/drug effects
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*Paraquat
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Pulmonary Edema/chemically induced/diagnosis/*drug therapy/metabolism
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Rats
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Rats, Sprague-Dawley
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Severity of Illness Index
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Superoxide Dismutase/metabolism
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Transforming Growth Factor beta1/metabolism
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X-Ray Microtomography