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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on December 17, 2004; DOI: 10.1124/jpet.104.078030

0022-3565/05/3131-379-388$20.00
JPET 313:379-388, 2005
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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Protection of Pirfenidone against an Early Phase of Oleic Acid-Induced Acute Lung Injury in Rats{boxs}

Shuang Mei, Wei Yao, Yuanjue Zhu, and Jinyuan Zhao

Research Center of Occupational Medicine, Third Hospital of Peking University and Department of Respiratory Medicine, Peking Union Medical College Hospital, Beijing, China

The potential role of PFD [5-methyl-L-phenyl-2-(1H)-pyridone], an antifibrotic compound with anti-inflammatory effects, in several models of acute lung injury (ALI) has gained increasing attention; however, the protective effect of PFD in oleic acid (OA)-induced ALI remains unknown. We hypothesized that PFD protects from OA-induced ALI in rats, and we hoped to obtain the optimum preclinical conditions with PFD in ALI. Sprague-Dawley rats were randomized into five groups (five rats per group): normal control group, OA-treated group (0.15 ml/kg), and three PFD-treated groups (20, 40, and 80 mg/kg p.o., respectively). Arterial blood gases, lung wet/dry weight ratio, and postmortem histological changes were determined 0.5, 1, 2, 6, and 24 h after OA challenge. Electron spin resonance spectroscopy was used for free radical detection and measurement. Experiments were examined based on the orthogonal test L4 (42) setting two factors (PFD dose and PFD valid time) with four different levels. The results of the orthogonal test showed that the sequence of effect of PFD was 0.5 h (oxygen radicals), 1 h (histological changes), 2 h (lung edema), and 6 h (partial pressure of oxygen) after OA challenge, and 40 mg/kg PFD was the most effective dose in this study. We conclude that PFD protects against OA-induced ALI in rats. The mechanism of these protective effects partly involves decrease of oxygen radicals. The data of this study proves that the orthogonal test will be a powerful method to help obtain the optimum experimental conditions with PFD in ALI in the future.

Received September 17, 2004; accepted December 6, 2004.

Address correspondence to: Jinyuan Zhao, 49 North Garden Road, Haidian District, Research Center of Occupational Medicine, the Third Hospital of Peking University, Beijing 100083 China. E-mail: zhaojinyuan{at}sina.com






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