18 research outputs found

    Pulmonary response to methylcyclopentadienyl manganese tricarbonyl treatment in rats: injury and repair evaluation

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    Methylcyclopentadienyl manganese tricarbonyl (MMT), an organometallic compound, used as an antiknock additive in fuels, may produce alveolar inflammation and bronchiolar cell injury. The aim of the experimental study on female rats was to determine by morphological examination and sensitive biomarkers, the course of the injury and repair process following a single i.p. injection of 5 mg/kg MMT. The animals were sacrificed 12, 24, 48 hours or 7 days post-exposure (PE). The first biochemical changes 12 h PE showed an increase in GSH-S-transferase (GST) activity in the lung parallel to the earliest observed morphological changes -vacuolation and swollen cytoplasm in type I pneumocytes. Alterations in type I pneumocytes were most prevalent in rat lung 24 h PE. Clara cells with dilated smooth endoplasmic reticulum membranes and cytoplasmic vacuolation could be observed. Compared to the values found for controls, Clara cell protein (CC16) in the bronchoalveolar lavage fluid (BALF) at 24 and 48 h PE decreased by 58% and 55%, respectively. At the same time (at 24 and 48 h), the total protein concentration in BALF increased 5 and 7 times, respectively. A significant rise in hyaluronic acid (HA) level was observed 24 and 48 h PE. Divided type II pneumocyte cells and Clara cells in their mitotic phase were observed in immunocytochemistry (detecting BrdU binding into DNA) 48 h PE. Seven days after MMT administration, fibroblasts, macrophages, collagen and elastin fibres could be seen in the alveolar walls as well as neutrophils, lymphocytes, and alveoli macrophages in the alveolar lumen. We conclude that injury and repair of bronchial epithelium cells, especially of Clara cells and type II pneumocyte cells, play an important part in MMT toxicity, probably depending on the antioxidant status of these cells. The sensitive biomarkers of CC16 and hyaluronic acid in BALF and serum reflect lung injury and indicate the time course of pulmonary damage and repair processes

    Lung permeability, antioxidant status, and NO2 inhalation: A selenium supplementation study in rats

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    Little is known about antioxidant status, selenium status in particular, and lung response to NO2, which acts as a proinflammatory air pollutant. The effects of a low selenium diet (1.3 mu g Se/d) with or without selenium supplementation were therefore studied in 128 Wistar rats, 2 mo old, male exposed to either acute (50 ppm, 30 min), intermittent subacute (5 ppm, 6 h/d, 5 d), intermittent long-term NO2 (1 ppm, 10 ppm, 6 h/d, 5 d/wk, 28 d), or normal atmospheric air (controls). Following sacrifice, measurements of lipid peroxidation ( thiobarbituric acid-reactive substances, chemiluminescence), antioxidative protective enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD], glutathione S-transferase [GST], ceruloplasmin), lung damage ( lactate dehydrogenase, alkaline and acid phosphatases), lung permeability ( total protein, albumin), and inflammation (cell populations), along with the determination of new biomarkers such as CC16 (Clara-cell protein), were performed in serum and bronchoalveolar lavage fluid (BALF). While selenium-supplemented animals had increased GPx activity in serum prior to inhalation experiments, they also had decreased BALF CC16, blood SOD, and GST levels. Nevertheless, the protective role of normal selenium status with respect to NO2 lung toxicity was evident both for long-term and acute exposures, as the increase in BALF total proteins and corresponding decrease in serum (indicating increased lung permeability) was significantly more pronounced in selenium-deficient animals. During the various inhalation experiments, serum CC16 demonstrated its key role as an early marker of increased lung permeability. These findings corroborate the important role of selenium status in NO2 oxidative damage modulation, but also indicate, in view of its negative impact on CC16, a natural anti-inflammatory and immunosuppressor, that caution should be used prior to advocating selenium supplementation
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