Ocytes. Because H2DCFDA fluorescence was attenuated by FeTMPyP treatment, increases
Ocytes. Because H2DCFDA fluorescence was attenuated by FeTMPyP treatment, increases were related to ONOO-. We further speculate that because the FeTMPyP-treated mice did not have to “cope” with the additional phagocyte ONOO-production, there was an overshoot in the overall lung antioxidant response, as evidenced by significant ( 2-fold) increases in lung GSH levels 24 h after DEP-exposure, relative to saline + airexposed mice (Figure 6A).Data are expressed as means (?SEM). Asterisk (*) Pemafibrate web indicates significantly different than saline-exposed mice ( p < 0.05).Discussion Maintaining redox balance in the lung is a dynamic process. It is especially challenging within the air passageways and alveolar spaces, where surface epithelial cells and resident phagocytes are exposed to -- and provide the first line of defense against -- a wide range of inhaled biologic (e.g., bacteria, viruses, allergens) and environmental agents (e.g., ozone, PM). In the present investigation, we used relatively simplistic in vitro and in vivo murine models of cytokine-induced epithelial and lung inflammation, respectively, to demonstrate the potential for NO (increased during inflammatory conditions) and ROS (increased as a consequence of traffic PM exposure) to "co-operate" to produce reactive oxidative as well as reactive nitrosative species (RNS) within PM-exposed lung cells. Specifically, we show that epithelial cells exposed to OC-rich DEP within an inflammatory microenvironment incur greater ROS/RNS burden and corresponding epithelial cytotoxicity; and thatManzo et al. Particle and Fibre Toxicology 2012, 9:43 http://www.particleandfibretoxicology.com/content/9/1/Page 8 ofTable 4 BAL fluid indices and lung glutathione ratios in saline- or cytomix-treated mice, 24 h after exposure to air or DEP for 2 consecutive daysAir N = 4/group Total Cells Macrophages Neutrophils Lymphocytes BAL fluid Biochemistries LDH (U/mL) Total Protein (g/mL) Albumin (g/mL) Lung GSH:GSSG 37.0 ?9.8 66.8 ?17.8 15.9 ?3.1 3.9 ?0.4 38.8 ?8.6 82.0 ?8.4 16.6 ?0.5 3.1 ?0.6 38.1 ?1.6 74.2 ?1.7 14.1 ?0.8 1.7 ?0.1 23.5 ?1.3 68.1 ?2.4 16.9 ?0.4 9.9 ?1.2* 43.7 ?6.7 88.1 ?16.9 14.7 ?1.7 9.2 ?1.8* 36.4 ?2.6 75.9 ?2.3 14.7 ?0.6 8.8 ?1.4* Saline 110 ?52 101 ?44 0.6 ?0.10 0.9 ?0.6 Cytomix 96.4 ?22 89.3 ?20 4.1 ?1.8 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27872238 3.0 ?0.7 FeTMPyP: Cytomix 109 ?11 101 ?11 5.5 ?1.5 3.0 ?1.2 Saline 84.8 ?21 83.2 ?21 0.4 ?0.1 1.2 ?0.5 BAL fluid cells per lung (x103) 107 ?35 96.4 ?33 7.5 ?2.6 2.8 ?0.7 84.3 ?10 78.0 ?9.1 4.7 ?0.8 1.6 ?0.7 DEP Cytomix FeTMPyP: CytomixData are expressed as the mean (?SEM) in saline- or cytomix-treated mice, 24 h after exposure to air or DEP for 2 consecutive days (2 mg/m3; 4 h/d ?2 d). Asterisk (*) indicates significantly different than saline-exposed mice ( p < 0.05).Figure 6 Day 4 comparison of mice. (A) lung glutathione levels and (B) ROS production in cells obtained by lung lavage in saline- or cytomix-treated mice, 24 h after exposure to air or DEP for 2 days (mean ?SEM; n = 4/group). Data are expressed as the mean nmol/g of lung tissue (?SEM) for GSH or GSSG. Significance ( p < 0.05) indicated by: * vs. DEP-cytomix. For ROS cell production, data are expressed as mean fold increase (?SEM) over saline + air-exposed mice. Significance ( p < 0.05) indicated by: * vs. air, cytomix, DEP; ** vs. cytomix + DEP.Manzo et al. Particle and Fibre Toxicology 2012, 9:43 http://www.particleandfibretoxicology.com/content/9/1/Page 9 ofcytomix + DEP-exposed mice incur greater ROS/RNS production in lung phago.