Lung Pathology In Rats Research Articles

Neutrophil elastase inhibitor suppresses oxidative stress in obese asthmatic rats by activating Keap1/Nrf2 signaling pathway.

The aim of this study was to detect the oxidative stress response in the rat model of obesity, asthma and obese asthma. Meanwhile, we aimed to investigate the inhibitory effect of neutrophil elastase inhibitor (NEI) on cellular oxidative stress in the body and whether it exerted an effect on the oxidative stress response in obese asthma through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 (Keap1/Nrf2) pathway. The obesity and asthma models were established using a total of 70 Sprague-Dawley (SD) rats. All rats were randomly divided into 7 groups. The rats with normal weight were divided into the control (CTR) group (n=10), asthma (ATM) group (n=10) and ATM+NEI group (n=10). Meanwhile, the obese rats were divided into the obesity (OBS) group (n=10), the OBS+NEI group (n=10), the OBS+ATM group (n=10) and the OBS+ATM+NEI group (n=10). After modeling, rats in NEI intervention groups were injected with Sivelestat (5 mg/kg) via the caudal vein twice a day for 1 week. The tests of cough sensitivity to capsaicin and bronchial responsiveness were performed 24 h after the last administration. Lung tissues of rats were collected for hematoxylin-eosin (HE) staining. Meanwhile, the levels of reactive oxygen species (ROS) in heart, lung and kidney tissues were detected via 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The activities of reduced glutathione (GSH), glutathione peroxidase (GSH-Px), H2O2 and total superoxide dismutase (T-SOD) in the heart, lung and kidney tissues were detected using the colorimetric method. The mRNA and protein expressions of Keap1 and Nrf2 messenger ribonucleic acid expressions in the heart, lung and kidney tissues were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting, respectively. NEI significantly improved the symptoms and lung pathology in rats with asthma. The level of ROS in the heart, lung and kidney tissues of the OBS group, ATM group and OBS+ATM group was significantly increased. However, NEI markedly inhibited the level of ROS in rats with asthma. The activities of antioxidant stress-related enzymes (reduced GSH, GSH-Px, H2O2 and SOD) in the heart, lung and kidney tissues of the OBS group, ATM group and OBS+ATM group were significantly decreased. However, NEI markedly promoted the activities of the related antioxidant enzymes in oxidative stress response in asthma rats. Besides, the Keap1/Nrf2 signaling pathway in the heart, lung and kidney tissues of the OBS group, ATM group and OBS+ATM group was significantly inhibited, while NEI activated the Keap1/Nrf2 signaling pathway in rats with asthma. NEI promotes the release of a variety of antioxidant factors, enhances the activity of antioxidant enzymes and improves the symptoms of rats with obese asthma. The possible underlying mechanism may be the activation of the Keap1/Nrf2 signaling pathway.

Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular (RV) hypertrophy (RVH), remodeling, and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology, and RV function. This model was chosen to mimic autologous MSC therapy. On day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. On day 14, rats were treated with 10(6) MSCs intravenously (MCT + MSC) or with saline (MCT60). MSCs were obtained from donor rats with PAH at 28 days after MCT. A control group received saline on days 1 and 14. On day 28, the RV function of recipient rats was assessed, followed by isolation of the lungs and heart. RVH was quantified by the weight ratio of the RV/(left ventricle + interventricular septum). MCT induced an increase of RV peak pressure (from 27 + or - 5 to 42 +/- 17 mmHg) and RVH (from 0.25 + or - 0.04 to 0.47 + or - 0.12), depressed the RV ejection fraction (from 56 + or - 11 to 43 + or - 6%), and increased lung weight (from 0.96 + or - 0.15 to 1.66 + or - 0.32 g), including thickening of the arteriolar walls and alveolar septa. MSC treatment attenuated PAH (31 + or - 4 mmHg) and RVH (0.32 + or - 0.07), normalized the RV ejection fraction (52 + or - 5%), reduced lung weight (1.16 + or - 0.24 g), and inhibited the thickening of the arterioles and alveolar septa. We conclude that the application of MSCs from donor rats with PAH reduces RV pressure overload, RV dysfunction, and lung pathology in recipient rats with PAH. These results suggest that autologous MSC therapy may alleviate cardiac and pulmonary symptoms in PAH patients.

Production of an Extracellular Toxic Complex by Various Strains of Pseudomonas Cepacia

Six isolates of Pseudomonas cepacia, representing various serotypes of the organism and possessing similar degrees of virulence in mice, were examined for their production of an extracellular toxic complex (ETC) in vitro. This compound is lethal for mice and produces extensive lung pathology in rats; it is composed of a surface carbohydrate antigen, lipopolysaccharide and protein. All six isolates produced the ETC. The LD50 values for the six ETC preparations ranged from 395 micrograms for strain 61g to 1750 micrograms for strain 90ee. Only two of the six ETC preparations contained ketodeoxyoctonate detectable by the methods used, and these two were the most toxic. Rabbit antiserum to the ETC of a serotype D strain could significantly protect mice only against serotype D strains. Examination of the various phases of growth of P. cepacia showed that there was extracellular release of the ETC beginning in the early logarithmic phase and continuing through the late stationary phase. The presence of the ETC in the supernatant fluids was due to release of this material rather than to cell lysis. In addition, at least one strain of P. cepacia was shown to produce an alginic acid-like compound.

The effect of high concentrations of oxygen on paraquat and diquat toxicity in rats.

High concentrations of oxygen are known to enhance the toxic effects of paraquat in the lung. We have examined the effects of paraquat (2.5 mg/kg or 20 mg/kg subcutaneously) and diquat (10 mg/kg or 20 mg/kg subcutaneously) on mortality and lung pathology in rats exposed to air or to an atmosphere of 85% oxygen. Our results show a 10-fold increase in mortality when paraquat is given to rats placed in 85% oxygen rather than air, but only a 2-fold increase in the lethality of diquat. Lung damage typical of early paraquat intoxication is seen following 20 mg/kg paraquat in air or oxygen, with damage to type I and type II alveolar cells. Selective damage to the type II cell is produced by lower levels of paraquat (2.5 mg/kg) and by 20 mg/kg diquat, both in 85% oxygen, other cell types showed little change. Lung damage is minimal following 2.5 mg/kg paraquat or 20 mg/kg diquat in air, or exposure to 85% oxygen alone. It is suggested that the type II cell may be the primary target cell for paraquat and diquat in the lung.

Petroleum hydrocarbon toxicity studies. IV. Animal and human response to vapors of Rubber Solvent

The suggested hygienic standard for inhalation of Rubber Solvent for man is 1.7 mg/liter (430 ppm) based upon inhalation studies with rats and dogs and the sensory response of human subjects. The LC50 for rats by 4 hr inhalation is 61 mg/liter (15,000 ppm). A concentration of 11 mg/liter (2800 ppm) caused no visible signs of discomfort in rats in 4 hr while for dogs the corresponding concentration was 5.9 mg/liter (1500 ppm). Cats exhibited signs judged to be indicative of central nervous system depression after a 4-hr inhalation of 49 mg/liter (12,000 ppm) but survived. At the highest concentration obtainable, 180 mg/liter (45,000 ppm), the Lt50 for rats was 4.3 min. Convulsions were produced in about 2 min. Rats and dogs inhaled measured concentrations of 7.9, 3.7, 1.9, and 0.0 mg/liter (2000, 930, 480, and 0.0 ppm) for 6 hr/day, 5 days/wk for 13 wk. The rats tolerated the highest level without any meaningful disturbances in the various criteria of effect that were followed. The only disturbing finding in the dogs was the dosage related granulation nodules found in the lungs. There is no evidence that the nodules were caused by the inhalation of Rubber Solvent but we cannot deny the condition may have been some-what exacerbated by the solvent vapor. This statement is based upon the 4-hr LC50 of 61 mg/liter (15,000 ppm) for rats and the lack of any similar lung pathology in rats that inhaled the same vapor: air mixtures in company with the dogs, for 13 wk. The odor of the solvent is detectable at 0.04 mg/liter (10 ppm) and 15-min periods of inhalation by human subjects resulted in good acceptance of the recommended hygienic standard.