Efore, conducted a dose response study and continued experiments at the dose level of 25

Efore, conducted a dose response study and continued experiments at the dose level of 25 g/mouse (0.5 mg/ml; Figure 2). A single and repeated aspiration model using PM combinations of JC, ZH, and ZH + NiSO4 (0.5 mg/ml) demonstrated significantly higher inflammation in the JC groupin comparison to control (Figure 2). Although it is possible that Ni was not the only driver of the observed response, the ZH + NiSO4 group emulated similar results as those of the JC group. No differences were seen in the one-time control versus the six-time Necrosulfonamide molecular weight exposure control.Serum markers indicative of inflammation and vascular dysfunctionSerum from mice treated with JC, ZH and ZH + NiSO4 had significantly higher IL-10 concentrations as compared to the control in the respected exposure duration (Figure 3A). Further VEGF was significantly greater in JC and ZH + NiSO4 in both exposure durations (Figure 3B). Statistically higher levels of TNF- were detected in the ZH + NiSO4 in comparison to ZH alone Figure 3E). No statistical differences were detected for IL-13, IL-6, CSF, and MCP-1 (Figure 3C,D,F,G).Cuevas et al. Particle and Fibre Toxicology (2015) 12:Page 4 ofFigure 2 Protein Analysis of Bronchoalveolar Lavage Fluid at an aspirated PM dose of 50 g. (A) Total protein leakage analysis, (B) cell differentiation and (C) cell counts in BALF 24-hour post-single aspiration (1X) or a repeated aspirations (6X) of PM2.5 (25 g = 0.5 mg/ml) from either JC, ZH, or ZH + NiSO4 (n = 8/grp; *p < 0.05; **p < 0.01; ***p < 0.001).No significant differences were detected at the one time point exposure compared to the respected controls. There were however, significantly higher concentrations of NO discovered between repeated exposure groups (Figure 4). More specifically, repeated exposures induced a significant decrease in NO concentration in the JC and the ZH + NiSO4 samples as compared to controls. There was also a time dependent difference indicated by a significantly lower NO concentration in the JC repeated group compared to the one-time exposure JC group.PM-induced vascular responsePE-induced contraction, SNP-induced relaxation or the half maximal effective concentration halfway between the baseline and maximum response values, respectively (Table 1 and Figure 5). Differences were seen in all groups PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27107493 when comparing maximum ACh-induced percent relaxation to controls however, only significant differences were seen in the JC and the ZH + NiSO4. In the presence of various inhibitors vascular function was improved (Figure 6). Greatest improvement was seen in the presence of NADPH oxidase inhibitor, VAS2780. ODQ and NAC showed no differences in either the treatment groups or in the control group (data not shown).Quantitative real time RT-PCR analysesSince constrictive responses to 120 mM KCl did not differ significantly among groups, agonist-induced responses were standardized using the 120 mM KCl responses. No significant differences were observed in the percentage of PE-induced pre-contraction between all groups and were therefore used to normalize vasodialtor (e.g. ACh, SNP) mediated responses. Results from repeated aspirations using PM from JC, ZH, and ZH + NiSO4 (0.5 mg/ml) indicated no statistical differences between groups for percentQuantitative real time RT-PCR results indicated a significantly higher mRNA expression of TNF- in mice treated with JC and ZH + NiSO4 PM as compared to control mice as well as when compared between exposure groups and exposure frequency (Figure.