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Fine- and coarse-sized titanium dioxide (TiO2) particles are considered to be relatively inert when inhaled. The goal of this study was to assess potential lung toxicity associated with well-characterized, non-dispersed rutile TiO2 nanorods (10 × 40 nm). In vitro bioreactivity of TiO2 nanorods was determined by electron spin resonance (ESR) to measure free radical production. To assess pulmonary effects in vivo, Sprague-Dawley rats were intratracheally instilled with saline, silica, or TiO2 nanorods (10 μg, 100 μg, or 1 mg/rat). On d 1, 3, and 6 posttreatment, left lungs were preserved for microscopy and histopathology, and lung lavage was performed on right lungs. Additional rats were treated with saline or TiO2 nanorods (100 μg or 1 mg/rat) on d 0, intratracheally inoculated with 5 × 105 Listeria monocytogenes on d 3, and bacterial clearance was assessed. ESR showed a significant concentration-dependent generation of hydroxyl radicals by TiO2 nanorods in the presence and absence of macrophages; however, the hydroxyl radical signals from TiO2 samples were low compared to silica. Rats exposed to 1 mg of TiO2 nanorods had significantly elevated levels of lung injury, inflammation, and lavage fluid monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 on d 1 and 3 that subsided by d 6, unlike the silica response that persisted. Immune cytokine secretion in the lung and bacterial clearance were not affected by preexposure to TiO2 nanorods. To summarize, non-dispersed TiO2 nanorods were found to induce radical formation and cellular oxidant production, and to generate transient and reversible pneumotoxic effects, and to not markedly alter pulmonary immune function. [ABSTRACT FROM AUTHOR]

Welders are exposed to fumes with different metal profiles. The goals of this study were to compare lung responses in rats after treatment with chemically different welding fumes and to examine the extrapulmonary fate of metals after deposition in the lungs. Rats were treated by intratracheal instillation (0.5 mg/rat, once a week for 7 weeks) with gas metal arc-mild steel (GMAW-MS) or manual metal arc-hardsurfacing (MMAW-HS) welding fumes. Controls were treated with saline. At 1, 4, 35, and 105 days after the last treatment, lung injury and inflammation were measured, and elemental analysis of different organs was determined to assess metal clearance. The MMAW-HS fume was highly water-soluble and chemically more complex with higher levels of soluble Mn and Cr compared to the GMAW-MS fume. Treatments with the GMAW-MS fume had no effect on toxicity when compared with controls. The MMAW-HS fume induced significant lung damage early after treatment that remained elevated until 35 days. Metals associated with each fume sample was cleared at different rates from the lungs. Mn was cleared from the lungs at a faster rate and to a greater extent compared to the other metals over the 105-day recovery period. Mn and Cr in the MMAW-HS fume translocated from the respiratory tract and deposited in other organs. Importantly, increased deposition of Mn, but not other metals, was observed in discrete brain regions, including dopamine-rich areas (e.g., striatum and midbrain). [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma membrane, whereas IFM are embedded between myofibrils. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations respond differently to a diabetic phenotype. Swiss-Webster mice were subjected to intraperitoneal injections of streptozotocin or citrate saline vehicle. Five weeks after injections, diabetic hearts displayed decreased rates of contraction, relaxation, and left ventricular developed pressures (P < 0.05 for all three). Both mitochondrial size (forward scatter, P < 0.01) and complexity (side scatter, P < 0.01) were decreased in diabetic IFM but not diabetic SSM. Electron transport chain complex II respiration was decreased in diabetic SSM (P < 0.05) and diabetic IFM (P < 0.01), with the decrease being greater in IFM. Furthermore, IFM complex I respiration and complex III activity were decreased with diabetes (P < 0.01) but were unchanged in SSM. Superoxide production was increased only in diabetic IFM (P < 0.01). Oxidative damage to proteins and lipids, indexed through nitrotyrosine residues and lipid peroxidation, were higher in diabetic IFM (P < 0.05 and P < 0.01, respectively). The mitochondria-specific phospholipid cardiolipin was decreased in diabetic IFM (P < 0.01) but not SSM. These results indicate that diabetes mellitus imposes a greater stress on the IFM subpopulation, which is associated, in part, with increased superoxide generation and oxidative damage, resulting in morphological and functional abnormalities that may contribute to the pathogenesis of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]