Lactate Dehydrogenase Activity In Lavage Fluid Research Articles

Protective effect of rutin against bleomycin induced lung fibrosis: Involvement of TGF-β1/α-SMA/Col I and III pathway.

Lung fibrosis is a progressive fatal lung disorder with significantly high mortality rates. Bleomycin (BLM) is one of the most commonly used chemotherapeutic agents for the treatment of several carcinomas. The most severe adverse effect of BLM is lung toxicity; therefore, BLM has been repeatedly reported to be considered amongst the most widely used agents for the induction of experimental lung fibrosis. In the current study, rutin has been investigated for its ability to ameliorate BLM-induced pulmonary fibrosis. BLM was instilled intratracheally and rutin was administered orally (50 and 100 mg/kg) for 3 weeks. Rutin significantly decreased lung/body weight index, bronchoalveolar lavage fluid lactate dehydrogenase activity, total cell count, macrophages, and lymphocyte counts. Rutin significantly decreased lung malondialdehyde content, increased lung glutathione content, superoxide dismutase activity, serum total antioxidant capacity, and decreased lung nitric oxide content. Moreover, rutin reduced expressions of transforming growth factor beta 1 and other fibrosis-related biomarkers (Col I, Col III, and α-SMA). In addition, rutin significantly ameliorated histological changes and prevented collagen deposition with the paralleled decrease in lung hydroxyproline content. In conclusion, rutin can be proposed to be a potential therapeutic agent for the management of lung fibrosis.

Transcriptomics analysis of lungs and peripheral blood of crystalline silica-exposed rats

Minimally invasive approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. The potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were exposed by inhalation to crystalline silica (15 mg/m3, 6 h/day, 5 days) and pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined at 32 weeks following termination of exposure. A significant elevation in bronchoalveolar lavage fluid lactate dehydrogenase activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 levels in the lungs showed pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression [>1.5-fold change and false discovery rate (FDR) p < 0.01] of 520 and 537 genes, respectively, in the lungs and blood of the exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica-exposed rats. The results of this study suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity.

Maternal respiratory sensitization and gestational allergen exposure does not affect subsequent pup responses to homologous or heterologous allergen

Evidence suggests that the predisposition towards atopy begins early in life. Maternal allergy has been associated with an increased risk of the development of allergic disease in offspring. Some studies suggest that the development of childhood atopy may also be influenced by prenatal allergen exposure. In this study, a respiratory allergen exposure model was used to determine the impact of maternal sensitization (with or without additional exposures during pregnancy) on subsequent pup responses to homologous or heterologous allergen. Female BALB/c mice received two intratracheal aspiration (IA) exposures to Metarhizium anisopliae crude antigen (MACA) or Hank’s buffered salt solution (HBSS) prior to breeding. Some mice also received three additional exposures during pregnancy. Control mothers did not receive treatment. Young adult offspring received three IA exposures to MACA, house dust mite extract (HDM) or HBSS. Offspring sensitized as young adults to either HDM or MACA developed an airway inflammatory response, including increased bronchoalveolar lavage fluid lactate dehydrogenase activity, total protein and total and differential cell counts compared to offspring exposed to HBSS. Increased airway responsiveness to methacholine was observed in pups treated with HDM but not with MACA. Maternal sensitization status (with or without gestational allergen exposure) had no effect on offspring response to either MACA or HDM. In conclusion, this study demonstrates that IA administration of MACA or HDM extract to young adult BALB/c mice induces the development of an inflammatory airway response. In contrast to previous reports, neither maternal sensitization nor gestational allergen exposure could be demonstrated to have a clear effect on offspring sensitization. This discrepancy may be a function of the respiratory sensitization and exposure protocol used in this study, which mimics natural sensitization more closely than do parenteral routes of exposure.

Thromboxane does not mediate pulmonary vascular response to monocrotaline pyrrole.

The possible involvement of thromboxane (Tx) in the pulmonary hypertension caused by monocrotaline pyrrole (MCTP) administration to rats was investigated by pharmacological intervention of Tx synthesis and action. The cyclooxygenase inhibitor, ibuprofen, at doses that inhibited platelet function and suppressed plasma Tx levels, did not attenuate MCTP-induced right ventricular hypertrophy or increased lung weight. Dazmegrel, an inhibitor of Tx synthetase, did not affect the MCTP-induced increase in lung weight or the elevation of lactate dehydrogenase activity or protein concentration in bronchopulmonary lavage fluid, despite significant reduction of the plasma concentration of Tx. Dazmegrel also did not alter the vascular leak or right ventricular hypertrophy due to administration of MCTP to rats. Finally, the Tx receptor antagonist L-640,035 was tested using a dosing regimen that reduced the increase in right ventricular pressure caused by a stable endoperoxide analogue in MCTP-treated rats. Cotreatment with L-640,035 did not attenuate the increase in lung weight, lavage fluid lactate dehydrogenase activity or protein concentration, or the pulmonary hypertension caused by MCTP. These results indicate that interference with Tx synthesis or action does not attenuate the toxic effects of MCTP and suggest that Tx is not necessary for the cardiopulmonary response to MCTP.

Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat

Chemically synthesized monocrotaline pyrrole (MCTP) was administered to adult male rats at a dose of 5 mg/kg in the tail vein. Controls received an equivalent volume of dimethylformamide vehicle. Rats were killed at 3, 5, 7, 10, and 14 days after treatment. Bronchopulmonary lavage fluid lactate dehydrogenase activity and lung weight were significantly elevated at 4 and 7 days, respectively, after MCTP, indicating that pulmonary damage had occurred. White blood cell count was elevated 7 days after treatment. Mean pulmonary arterial pressure was also first elevated in treated (22 +/- 3 mmHg) compared with control (16 +/- 1 mmHg) animals 7 days after treatment. Right ventricle-to-left ventricle plus septum weight ratios were significantly increased in treated (0.429 +/- 0.015) vs. control (0.320 +/- 0.015) animals 14 days after treatment. Development of right heart enlargement correlated with a shift in the QRS complex mean electrical axis in the frontal plane of the electrocardiogram. These results indicate that MCTP produces effects similar to that caused by monocrotaline, that pulmonary arterial pressure increases from control levels between 5 and 7 days after treatment, and that measurement of mean electrical axis of the electrocardiogram may be a useful, noninvasive method to monitor MCTP-induced cardiac changes in vivo.

Effect of pneumotoxicants on lactate dehydrogenase activity in airways of rats

To assess the usefulness of monitoring changes in lactate dehydrogenase (LDH) activity in the cell-free fraction of bronchopulmonary lavage fluid as an indicator of pulmonary injury, several toxicants were administered to rats using treatment regimens which have been shown previously to result in histopathologically demonstrable pneumotoxicity. For all of the toxicants employed except exposure to 1 atm O 2, treatment did not affect recovery of lavage fluid from the lung. Lavage fluid LDH activity was elevated following treatment with paraquat, bromobenzene, and oxygen. Administration of monocrotaline using a treatment regimen which results predominantly in lung injury also produced elevated LDH activity in lavage fluid; however, treatment with this same compound using a regimen which results predominantly in hepatic injury failed to elevate lavage fluid LDH activity but resulted in a more pronounced increase in LDH activity in plasma. Similarly, the hepatotoxicant, carbon tetrachloride, produced a marked increase in plasma LDH activity without affecting that of the lavage fluid. The sensitivity of this method in detecting increased LDH activity was minimally dependent upon the volume of fluid used for lavage or on the number of successive lavages used for analysis. It appears to be useful as a rapid screening test for detecting lung injury from chemicals which are pneumotoxic following inhalation or systemic administration.