Inhibition of experimental acute pulmonary inflammation by pirfenidone

Spond, Jeffrey; Case, Natalie R.; Chapman, Richard W.; Crawley, Yvette; Egan, Robert W.; Fine, Jay S.; Hey, John A.; Kreutner, William; Kung, Ted T.; Wang, P; Minnicozzi, Michael

doi:10.1016/s1094-5539(03)00026-9

Cited by 46 publications

(27 citation statements)

References 36 publications

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“…Hormonally and immunologically guinea pigs are more like humans than other rodents; thus they are often used to model human infectious diseases [58]. Although rats are not as similar to humans they have been used to study a range of diseases such as emphysema [59], influenza [60] and pulmonary fibrosis [61]. Other systemic diseases such as diabetes can be induced in rats by administration of streptozocin [62].…”

Section: Animal Modelsmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

130

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Section: Animal Modelsmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

130

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“…Therefore, we conclude the mechanism of these protective effects of PFD partly involves suppression of oxygen radicals in lung tissues. PFD (10 and 30 mg/kg) was documented to exert a dosedependent anti-inflammatory in the models of endotoxininduced lung injury (Spond et al, 2003). A top dose of PFD (30 mg/kg) did not completely inhibit the recruitment of inflammatory cells.…”

Section: Protection Of Pfd From An Early Phase Of Ali By Oa In Rats 385mentioning

confidence: 95%

“…Thus, an initial small quantity of free radicals can stimulate a cascade of events resulting in a significant increase in neutrophil recruitment and inflammatory mediators and the exacerbation of lung injuries via positive feedback loops. We speculate that PFD suppresses production of oxygen radicals and then inhibits nuclear factor-B (Tsuchiya et al, 2004) and nuclear factor-B induced several cytokines such as tumor necrosis factor-␣ relevant to ARDS pathology (Iyer et al, 2000;Corbel et al, 2001;Oku et al, 2002;Spond et al, 2003), which ameliorates lung edema and gas exchange. Therefore, we conclude the mechanism of these protective effects of PFD partly involves suppression of oxygen radicals in lung tissues.…”

Section: Protection Of Pfd From An Early Phase Of Ali By Oa In Rats 385mentioning

confidence: 99%

“…Thus, future studies should focus on newer forms of therapy and, if possible, the early course of the disease. PFD [5-methyl-Lphenyl-2-(1H)-pyridone, Deskar; Tocris Cookson Inc., Ellisville, MO], a new experimental drug, was chosen as a therapeutic agent for ALI and ARDS in this study which has shown that PFD could attenuate the severity of experimental ALI by lipopolysaccharide challenge (Cain et al, 1998;Corbel et al, 2001;Oku et al, 2002;Spond et al, 2003) and bleomycin induction (Iyer et al, 1995(Iyer et al, , 1998(Iyer et al, , 2000Schelegle et al, 1997;Mansoor et al, 1999).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Mei

Yao²,

Zhu³

et al. 2004

J Pharmacol Exp Ther

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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. SpragueDawley 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 (4 2 ) 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.

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“…12 In addition, it has been suggested that pirfenidone has anti-inflammatory properties, so the exact mechanism of any benefit for pirfenidone in IPF is currently unclear. 13 …”

Section: How May Pirfenidone Influence the Pathophysiology Of Ipf?mentioning

confidence: 99%