The effects of organic extract of diesel exhaust particles on ischemia/reperfusion-related arrhythmia and on pulmonary inflammation.
Since our previous study demonstrated the exacerbation of acute myocardial ischemia/reperfusion (AMIR)-related arrhythmia by intratracheal instillation (IT) of diesel exhaust particles (DEP), the influence of IT with extracts of DEP in organic solvents on AMIR-related arrhythmia was examined in rats. Oxidative activity in a non-biological assay system and proinflammatory activity in mice of DEP extracts were examined. The dichloromethane-soluble fraction (DMSF) of DEP was further fractionated into n-hexane-soluble (n-HSF) and n-hexane-insoluble (n-HISF) fractions. The oxidative activities of the fractions evaluated by dithiothreitol assay were ranked as follows: n-HISF>DMSF>n-HSF. Twenty-one to 34 hr after IT, the AMIR experiment was performed. Exacerbation of AMIR-related arrhythmia and increased reperfusion-related mortality were observed only in rats treated with DMSF. In fact, n-HSF and n-HISF did not affect arrhythmia up to 5 mg/kg. Twelve hr after IT, a significant increase in neutrophil count was observed only with DMSF. The levels of granulocyte colony-stimulating factor and interleukin-6 in bronchoalveolar lavage fluid were significantly elevated in the group treated with DMSF, while neither, n-HSF nor n-HISF, affected the level of cytokines up to 5 mg/kg. In fact, tumor necrosis factor-alpha, IL-10 and granulocyte-macrophage colony-stimulating factor were unchanged with any of the fractions. In conclusion, exacerbation of AMIR-related arrhythmia by DMSF suggests the contribution of non-particle components of DEP to arrhythmia while the component contributed to the effects did not become clear. Furthermore, it is confirmed that exacerbation of AMIR-related arrhythmia is accompanied by an increased neutrophil count in the circulatory blood.
Yokota
Syunji
S
Laboratory of Toxicology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan. yokota.s@fdsc.or.jp.
Ohara
Naoki
N
Kobayashi
Takahiro
T
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity; D016207:Cytokines / Q000276:immunology; D006586:Hexanes / Q000737:chemistry; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D007958:Leukocyte Count; D008171:Lung Diseases / Q000209:etiology / Q000276:immunology*; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000276:immunology; D012997:Solvents / Q000737:chemistry; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D045424:Complex Mixtures; D016207:Cytokines; D006586:Hexanes; D012997:Solvents; D001335:Vehicle Emissions; C026385:n-hexane; D008752:Methylene Chloride