LDH In Bronchoalveolar Lavage Fluid Research Articles

Comparative Pulmonary Protective Efficacy of Amifostine and it’s Analogue S-2(2-aminoethylamino)ethyl Phenyl Sulfide (DRDE-07) against Sulphur Mustard Induced Oxidative Stress and Inflammation in Female Mice

Aim: The present study was undertaken to investigate the comparative pulmonary protective efficacy of Amifostine (S-2[3-aminoprophylamino] ethyl phosphorothioate) and its analogues DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulfide) against sulfur mustard toxicity in mice. Materials and Methods: Twenty female mice were divided into four groups: Control, SM group animals were percutaneously exposed to 16.2 mg/kg. The third and fourth group of animals received amifostine and DRDE-07 (210 and 250 mg/kg respectively) through the oral route, 30 min before SM exposure. The clinical symptoms and body weight changes were observed daily and sacrificed on 7th day. Bronchoalveolar lavage fluid (BALF) and lung tissuewere collected for biochemical and histopathological studies. The following biochemical endpoints were studied in BALF (total cell count, lactate dehydrogenase, protein content, β-glucuronidase activity, MMP-2, 9 activityand FSH) whereas reactive oxygen species (ROS), reduced glutathione (GSH), lipid peroxidation, superoxide dismutase, catalase and myeloperoxidase activity was measured in lung tissue. The above biochemical observations are also supported by histopathology studies. Results: Dermal exposure to SM significantly reduced body weight. The significant increase in BALF LDH leakage, protein content, cell number and MMPs activity in the SM exposed animals suggest disruption of endothelial barrier in the lung (p<0.05). Significant ROS generation (p<0.05) was observed in lung tissue of SM group which results in a significant decrease in SOD GSHand CAT and an increase in MDA (p<0.05). These alterations in BALF as well in lung tissue due to SM exposure was significantly prevented by the pretreatment of amifostine and DRDE-07 (p<0.05). The histopathological observations also support the above results. The above results indicate that the preventive efficacy of DRDE-07 is better than amifostine. Conclusion: The percutaneous SM exposure-induced pulmonary damages were significantly protected by DRDE-07 than amifostine in mice.

N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis

BackgroundInflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. Materials and methodsFifty-two adult male Sprague–Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. ResultsInduction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P < 0.05) and inflammation (0.6 ± 0.2 versus 1.29 ± 00.3, P < 0.05) scores. ConclusionsAdministration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP.

Synergistic effects of exposure to concentrated ambient fine pollution particles and nitrogen dioxide in humans

Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.Objectives: Determine if simultaneous exposure to PM and NO2 results in synergistic interactions.Materials and methods: Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO2, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM2.5CAPs, 89.5 ± 10.7 µg/m3), or NO2+PM2.5CAPs for 2 h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18 h after exposure. Bronchoalveolar lavage (BAL) was performed 18 h after exposure.Results: NO2 exposure alone increased cholesterol and HDL 18 h after exposure, decreased high frequency component of HRV one and 18 h after exposure, decreased QT variability index 1 h after exposure, and increased LDH in BAL fluid. The only significant change with PM2.5CAPs was an increase in HDL 1 h after exposure, likely due to the low concentrations of PM2.5CAPs in the exposure chamber. Exposure to both NO2 and PM2.5CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO2 or PM2.5CAPs alone, suggesting possible interactions between the two pollutants.Discussion and conclusions: NO2 exposure may produce and enhance acute cardiovascular effects of PM2.5CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.

Hypertensive Rats are Susceptible to TLR4-Mediated Signaling Following Exposure to Combustion Source Particulate Matter

Toll-like receptor 4 (TLR4) has been shown to play a role in cell signaling that results in neutrophilic inflammation in response to lipopolysaccharide and respiratory syncytial virus infection. TLR4 also interacts with CD14, which upon complex formation triggers TLR4-associated signaling pathways to produce a proinflammatory response. This mechanism results in the activation of NF-κ B and subsequent inflammatory gene induction. In order to determine the effect of combustion source particle matter (PM), rich in zinc and nickel but with negligible endotoxin, on a possible activation of TLR4-mediated cell signaling and inflammation, we intratracheally (IT) instilled 3.3 mg/kg of PM into 12-w-old healthy male Wistar Kyoto (WKY) and susceptible spontaneously hypertensive (SH) rats. Inflammation, inflammatory-mediator gene expression, bronchoalveolar lavage fluid (BALF) protein and LDH, TLR4 and CD14 protein, and NF-κ B activation in the lung were determined after 24 h. Dose-response data (0.0, 0.83, 3.33, and 8.3 mg/kg PM) for BALF LDH were obtained as a marker of lung cell injury in SH rats. BALF neutrophils, but not macrophages, were significantly increased in the PM-exposed WKY and SH rats. SH rats showed a greater PMN increase than WKY rats. Similarly, BALF protein and LDH levels were also increased following PM exposure but to a significantly greater extent in SH rats. Plasma fibrinogen was increased only in SH rats exposed to PM. The increased inflammation seen in PM-exposed SH rats was accompanied by a significant increase in TLR4 protein in the lung tissue, which was primarily localized in alveolar macrophages and epithelial cells. CD14 was also increased by PM exposure in both SH and WKY rats but was significantly greater in the SH rats. These increases were associated with greater translocation of NF-κ B in the lungs of SH rather than WKY rats. This was accompanied by increased macrophage inhibitory protein (MIP)-2 mRNA expression at 24 h of exposure. These data suggest that the increased inflammation in the lungs of PM-exposed SH rats compared to WKY rats is accompanied by an increase in TLR4-mediated cell signaling. Thus, one of the mechanisms for greater susceptibility of SH rats to PM exposure may involve an increased activation of the TLR4 signaling pathway.

Serum Clara cell protein (CC16): a new valid marker of the distal airway damages caused by air pollutants in rats.

Cell count, LDH, total protein, Clara cell protein (CC16) and lysozyme in bronchoalveolar lavage fluid (BAL) and serum were determined in rats. 30-50 ppm sulfur dioxide for 4 h. 12 h and 2 week exposure didn't produce any change of above parameters. 1.0 ppm, 0.5 ppm, 0.38 ppm, 0.25 ppm and 0.20 ppm ozone for 7 h exposure tests were performed. CC16, total protein and LDH in BAL had significantly changes in BAL in ozone groups. Only serum CC16 showed significant increase among ozone groups. Both BAL and serum CC16 were of the best exposure-response relationship with ozone concentration. The change of BAL fluid reached high peak 18-24 h after ozone exposure. Serum CC16 seemed to be a valid marker of the distal airway damages caused by air pollutants.