The effects of organic extract of diesel exhaust particles on ischemia/reperfusion-related arrhythmia and on pulmonary inflammation

Abstract

-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-α, 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.

Transient Receptor Potential Vanilloid-1 (TRPV1) Is a Mediator of Lung Toxicity for Coal Fly Ash Particulate Material

“…It is noteworthy that the 250 g i.t. dose used in this study substantially higher than what occurs through most short-term environmental exposures, but it is within the range used previously for intrathecal instillations of DEP, CFA1-like materials, and other PM materials (Ogugbuaja et al, 2001;Ernst et al, 2002;Takano et al, 2002a,b;Gilmour et al, 2004;Yokota et al, 2008;Costa et al, 2010) and could approximate a total daily dose under some circumstances. Regardless, this exposure should allow a general assessment of whether TRPV1 plays an integral role in mediating select toxicologically relevant outcomes in the mouse lung or not.…”

Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases

“…Several of the studies cited have made the association with inhalation of fine particles rather than with the PAHs (Costello et al, 2013; Toren et al, 2007). It has been shown, however, that the toxicity of the particles is due to the adsorption of the PAHs on the solid particles and the subsequent partitioning from such particles onto and through lipophilic membranes (Yokota et al, 2008). The fine particles serve as vehicles to deliver the PAHs deep into the lungs, where these compounds are absorbed.…”

Lipophilic chemical exposure as a cause of cardiovascular disease

“…al., 2013; Toren et al , 2007). It has been shown, however, that the toxicity of the particulates is due to the adsorption of the PAHs on the solid particles and the subsequent partitioning from such particles onto and through lipophilic membranes (Yokota et al , 2008). The fine particles serve as vehicles to deliver the PAHs deep into the lungs, where these compounds are absorbed.…”

“…These include persistent organic pollutants (POPs) – polychlorinated bipehenyls (PCBs) (Lind & Lind 2012; Lind et al , 2012a; Ha et al , 2007; Everett et al , 2011; Sjoberg et al , 2013), organochlorine pesticides (OCs) (La Merrill et al , 2013; Lind & Lind, 2012; Lind et al , 2012a; Valera et al , 2012), dioxins and furans (Lind & Lind, 2012; Lind et al , 2012a; Ha et al , 2007; Brown 2008; Everett et al , 2011), polybrominated biphenyl ethers (PBDEs) used as fire retardants (Lind & Lind, 2012; Lind et al , 2012a; Ha et al , 2007) and esters of perfluorooctanoic acid (PFOEs), widely used in cleaning products (Shankar et al , 2012; Min et al , 2012; Holtcamp, 2012); bisphenol A, widely used in the manufacture of plastic food containers and other applications, (Lind & Lind, 2012; Melzer et al , 2010; 2012a, b; Shankar et al , 2012; Bae et al , 2012; Olsen et al , 2012a, b); and phthalates, widely used as plasticizers for polyvinyl chloride, (Singh & Shoei-Lung, 2011; Lind & Lind, 2011; 2012; Olsen et al , 2012a, b), which are exuded from plastics; low molecular weight aliphatic and aromatic hydrocarbons (LMWHCs) and their chlorinated products which evaporate from gasoline, adhesives, paints and household products (ATSDR, 2001; Morvai et al , 1976; Capron & Logan, 2009; Tsao et al , 2011; Xu et al , 2009; Tsai et al , 2010; Kotseva & Popov, 1998; Rosenman, 1979; Rufer et al , 2010); and polynuclear aromatic hydrocarbons (PAHs) which come from primary and secondary tobacco smoke and fuel combustion (Wellenius et al , 2012; Martinelli et al , 2013; Liu et al , 2013). Mechanisms of action have been suggested for some of these chemicals, but to date no one mechanism can account for the cardiovascular toxicity of this diversified group of chemicals which differ in widely in structure, chemical properties and reactivity (Yokota et al , 2008; Toren et al , 2007; Burstyn et al , 2005; Iwano et al , 2005; Mustafic et al , 2012; Wichmann et al , 2013; Brunekreef et al , …”