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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Shuang Mei, Wei Yao, Yuanjue Zhu and Jinyuan Zhao
Journal of Pharmacology and Experimental Therapeutics April 2005, 313 (1) 379-388; DOI: https://doi.org/10.1124/jpet.104.078030
Shuang Mei
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Wei Yao
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Yuanjue Zhu
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Jinyuan Zhao
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Abstract

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.

Footnotes

  • This work was supported by grants from the National Science Foundation Committee (NSFC, 30170799) and Ph.D. Research Foundation of Education Ministry (20010001092) of China.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.104.078030.

  • ABBREVIATIONS: ARDS, acute respiratory distress syndrome; ALI, acute lung injury; OA, oleic acid; ROS, reactive oxygen species; ESR, electron spin resonance; PFD, 5-methyl-l-phenyl-2-(1H)-pyridone, pirfenidone; PBN, α-phenyl-N-tert-butyl nitrone; PaW2, partial pressure of carbon dioxide; PO2, partial pressure of oxygen.

  • ↵ Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

    • Received September 17, 2004.
    • Accepted December 6, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 382 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 382, Issue 3
1 Sep 2022
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Shuang Mei, Wei Yao, Yuanjue Zhu and Jinyuan Zhao
Journal of Pharmacology and Experimental Therapeutics April 1, 2005, 313 (1) 379-388; DOI: https://doi.org/10.1124/jpet.104.078030

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

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

Shuang Mei, Wei Yao, Yuanjue Zhu and Jinyuan Zhao
Journal of Pharmacology and Experimental Therapeutics April 1, 2005, 313 (1) 379-388; DOI: https://doi.org/10.1124/jpet.104.078030
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