Pulmonary Injury In Rats Research Articles

Establishment of Nano-ITO induced rat model of indium lung disease and exploration of its pathological characteristics

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1β, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.

A new approach for the treatment of bleomycin-induced rat pulmonary injury by combined protein fraction of major royal jelly protein 2 and its isoform X1

Nowadays, royal jelly (RJ) has gained great interest as a functional food due to its valuable pharmacological effects. We investigated the therapeutic potency of combined protein fraction (PF50) of major RJ protein 2 and its isoform X1 on bleomycin (Bleo)-induced pulmonary injury in rats. Our study examined the impact of PF50 on pulmonary oxidative and inflammatory stress as well as smooth muscle alpha-actin (α-SMA). In addition, the predicted impacts of this PF on the activity of matrix metalloproteinase (MMP)− 8 and 15-prostaglandin dehydrogenase (15-PGDH) and the E-type prostanoid 2 (EP2) and IL-13 α2 subunit (IL13α2R) receptors, were evaluated using molecular docking. The results showed that PF50 reduced pulmonary inflammatory cells and their secreted pro-inflammatory mediators, including NF-κB, IKK, IL-4, IL-6, and NO. Additionally, the levels of IgE and mucin were diminished after treatment with PF50. Moreover, PF50 treatment improved pulmonary oxidative stress indices such as lipid peroxidation, GSH, SOD, and GPX. The histopathological findings, chest conventional X-ray, and immunohistochemistry of α-SMA confirmed the ameliorating effect of PF50. The docking outcomes reported the probable competitive inhibitory influence of PF50 on MMP-8 and a postulated blocking effect on EP2 and IL13α2R. Thus, PF50 could be a novel approach for treating pulmonary injuries.

Nilotinib alleviates paraquat-induced hepatic and pulmonary injury in rats via the Nrf2/Nf-kB axis

BackgroundParaquat (PQ, 1,1′-dimethyl-4-4′-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture. It exerts its toxic effects mainly as a result of its redox cycle via the production of superoxide anions in organisms, leading to an imbalance in the redox state of the cell causing oxidative damage and finally cell death. The aim of this study was to estimate the beneficial protective role of nilotinib (NIL) on PQ-induced hepatic and pulmonary toxicity in rats. MethodsMale wistar rats were randomly divided into four groups, namely control, PQ (15 mg/kg), PQ plus NIL (5 mg/kg) and PQ plus NIL (10 mg/kg). NIL (5 and 10 mg/kg/day) was taken by oral syringe for five days followed by a single intra-peritoneal administration of PQ (15 mg/kg) on sixth day. ResultsPretreatment with NIL relieved the histological damage in liver and lung tissues and improved hepatic biochemical markers. It significantly (p < 0.05) reduced serum levels of ALT, AST, ALP, Y-GT and total bilirubin while increased that of albumin. Meanwhile, NIL significantly (p < 0.05) reduced oxidative stress markers via reduction of malondialdhyde (MDA) and elevation of glutathione (GSH) contents in liver and lung tissues. In addition, it significantly (p < 0.05) decreased the inflammation by reducing hepatic and pulmonary tumor necrosis factor alpha (TNF-α) and nuclear transcription factor kappa B (NF-KB/p65) contents. Nilotinib also down-regulated apoptosis by reducing cysteinyl aspartate-specific proteinase-3 (caspase-3). Furthermore, it upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) in liver and lung tissues. SignificanceNIL suppressed PQ-induced inflammation, oxidative stress and apoptosis in liver and lung tissues by modulating Nrf2/Nf-kB axis.

Dissecting the effects of paraquat-induced pulmonary injury in rats using UPLC-Q-TOF-MS/MS-based metabonomics.

Paraquat (PQ) is a toxic compound that selectively accumulates in the lungs, inducing severe pulmonary inflammation and fibrosis. However, data on the metabolomic changes induced by the PQ remain scant. This study aimed to determine the metabolic changes in Sprague-Dawley rats subjected to PQ using UPLC-Q-TOF-MS/MS. We established groups of PQ-induced pulmonary injury rats for 14 or 28days. Our data showed that PQ decreased the survival of the rats and induced pulmonary inflammation at day 14 or pulmonary fibrosis at day 28. There was upregulation of IL-1β expression in the inflammation group as well as upregulation of fibronectin, collagen and α-SMA in the pulmonary fibrosis group. OPLS-DA revealed differential expression of 26 metabotites between the normal and the inflammation groups; 31 plasma metabotites were also differently expressed between the normal and the fibrosis groups. There was high expression of lysoPc160-, hydroxybutyrylcarnitine, stearic acid, and imidazolelactic acid in the pulmonary injury group compared to the normal group. Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. This study gives insights into the mechanisms of PQ-induced lung injury and highlights the potential therapeutic targets. The effect of PQ on lung injury in rats was detected by metabonomics, and the possible metabolic mechanism was investigated by KEGG analysis. OPLS-DA revealed the differential expression of 26 metabotites and 31 plasma metabotites between the normal and the pulmonary injury groups. Metabolomics analysis confirmed that the PQ-induced lung injury was not only related to the aggravation of inflammation and apoptosis but also to mediated histidine, serine, glycerophospholipid, and lipid metabolism. Oleoylethanolamine, stearic acid, and imidazolelactic acid are potential molecular markers in PQ-induced pulmonary injury.

Protective Potential of Saussurea costus (Falc.) Lipsch. Roots against Cyclophosphamide-Induced Pulmonary Injury in Rats and Its In Vitro Antiviral Effect.

Diseases and infections of the respiratory tract are common global causes of morbidity and mortality. Our study attempts to elucidate a novel remedy for respiratory ailments, in addition to identifying and quantifying the metabolites of Saussurea costus root extract (SCRE) using HPLC. Then, in vitro antiviral and in vivo lung protective effects were elucidated. The in vitro antiviral potential of SCRE was analyzed via plaque assay against the low pathogenic human coronavirus (HCoV-229E) and human influenza virus (H1N1). The value of the half maximal inhibitory concentrations (IC50) of SCRE against HCoV-229E and H1N1 influenza virus were 23.21 ± 1.1 and 47.6 ± 2.3 µg/mL, respectively. SCRE showed a histological improvement, namely a decrease in inducible nitric oxide synthase (iNOS) and caspase-3 immunoexpression in in vivo cyclophosphamide (CP)-induced acute lung injury (ALI). Moreover, there was a considerable decline in microRNA-let-7a gene expression and a significant rise in heme oxygenase-1 (HO-1) gene expression, with a marked decrease in the malondialdehyde (MDA) level. Molecular docking studies revealed that the major constituents of SCRE have a good affinity for caspase-3, HO-1, and iNOS proteins. In conclusion, a traditional plant SCRE could be a promising source of novel therapeutic agents for treating and protecting respiratory tract diseases. More future investigations should be carried out to reveal its efficacy clinically.

Dysregulation of Inflammatory Cytokines by Endotoxin Induces Tissue iNOS Expression and Pulmonary Injury in Rats

Dysregulation of Inflammatory Cytokines by Endotoxin Induces Tissue iNOS Expression and Pulmonary Injury in Rats

Influence of Intestinal Lymphatic Ligation on Pulmonary Injury in Rats with Severe Acute Pancreatitis.

The present study explored the mechanisms involved in intestinal lymphatic ligation in rats with severe acute pancreatitis (SAP). Male Sprague Dawley rats were randomly divided into 4 groups: saline group, saline+ligation group, SAP group, and SAP+ligation group. Rats in the SAP group were administered sodium taurocholate solution. Isolated mesenteric lymph duct ligation was administered to the saline+ligation and SAP+ligation groups. Endotoxin (ET), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), myeloperoxidase (MPO), and superoxide dismutase (SOD) were detected. Nuclear factor-κB (NF-κB) and intercellular cell adhesion molecule-1 (ICAM-1) proteins were observed. The mRNA of inducible nitric oxide synthase(iNOS) and Toll-like receptor 4 (TLR4) was detected by PCR. Pathomorphological analysis showed that necrosis was present in the lung of rats in the SAP group, but only mild lesions in the SAP+ligation group. ET, NO, TNF-α, and IL-1 in the serum and lung tissue were significantly decreased and MPO was increased in the SAP+ligation group as compared with the SAP group. However, MPO was increased. The expression of NF-κB and ICAM-1, either iNOS or TLR4, was upregulated in the SAP group, but downregulated in the SAP+ligation group. Intestinal lymph duct ligation prevented ET translocation, the release of inflammation factors, and inflammation injury. The intestinal lymph duct ligation could alleviate SAP-induced pulmonary injury by suppressing NF-κB activation in rats.

Modulation of COX-2 and NADPH oxidase-4 by alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats

AimsThis study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats. Main methodsEighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR. Key findingsAdministration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4. SignificanceALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

The Effects of Dexmedetomidine and Ketamine on Oxidative Injuries and Histological Changes Following Blunt Chest Trauma.

BackgroundThe objective of this research was to evaluate the oxidative and histopathological effects of dexmedetomidine and ketamine on the pulmonary contusion model resulting from blunt chest trauma.MethodsRats were randomly assigned to 5 equal groups (n=6): control group (Group C), pulmonary contusion group (Group PC), PC-dexmedetomidine group (Group PC-D), PC-ketamine group (Group PC-K), and PC-dexmedetomidine + ketamine (Group PC-D+K). The PC was performed by dropping a weight of 500 g (2.45 Joules) from a height of 50 cm. In Group PC-D, after chest trauma, dexmedetomidine (100 µg/kg) was administered intraperitoneally. In Group PC-K, after chest trauma, ketamine (100 mg/kg) was administered intraperitoneally. In Group PC-D+K, dexmedetomidine and ketamine were administered together. At the end of the 6th hour, rats were sacrificed. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activities, neutrophil infiltration/aggregation, and thickness of the alveolar wall were evaluated.ResultsMDA levels were significantly higher in Group PC than Groups C, PC-D, and PC-D+K. SOD enzyme activity was significantly higher in Group PC than Groups C, PC-D, and PC-D+K. In addition, neutrophil infiltration/aggregation and total pulmonary injury scores were significantly higher in Group PC than in other groups, and the thickness of the alveolar wall was significantly higher in Group PC compared to Groups C, PC-D, and PC-D+K. MDA level, SOD enzyme activities, neutrophil infiltration/aggregation, and thickness of alveolar wall were similar in PC-D and PC-D+K groups.ConclusionDexmedetomidine and dexmedetomidine+ketamine have protective effects on blunt chest trauma but no protective effect was observed when ketamine was administered alone. We concluded that the administration of dexmedetomidine and ketamine after contusion is beneficial against pulmonary injury in rats.

Curcumin Prevents Cyclophosphamide-Induced Lung Injury in Rats by Suppressing Oxidative Stress and Apoptosis

Curcumin (CUR) has been used since ancient times to treat several ailments as it possesses many pharmacological activities. This study intended to explore the mechanism underlying the protective effects of CUR in remodeling oxidative stress and apoptotic signals in cyclophosphamide (CP)-induced pulmonary injury in albino rats. CUR was administered at a dose of 300 mg/kg/day for 7 days and on the seventh day a single dose of CP (200 mg/kg) was given. Histopathological and ultrastructural examinations of CP-intoxicated rats showed complete alveolar obstruction, thickened inter-alveolar septa, enlarged blood vessels, severe inflammatory edema with pyknotic nuclei, and disappearance of cytoplasmic organelles. Significant increases in caspase-3, malondialdehyde (MDA), and protein carbonyl (PCO) and significant decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) were observed. In contrast, rats that received CUR showed clear and empty lumina with single row of pneumocytes, disappearance of edema, and no interstitial electron dense bodies in rats’ lung tissues. Additionally, CUR significantly reduced caspase-3, MDA, and PCO and increased SOD and GPx. In conclusion, these findings revealed the protective effects of CUR against CP-induced pulmonary injury in rats through suppressing oxidative damage and apoptosis.

Protective and anti-inflammatory effect of selenium nano-particles against bleomycin-induced pulmonary injury in male rats

Pulmonary fibrosis (PF) is an interstitial lung disease, in which the exact pathologic mechanisms are not fully understood. Drug trials for the treatment of PF have shown disappointing results and controversial. Recently, selenium nanoparticles (SeNPs) have received great attention for potential use in treatments, due to high bioactivity features and lower toxicity. This study evaluated the protective effect of SeNPs against pulmonary injury induced by bleomycin (single dose, 4 mg/kg, intratracheal) in male rats in early and late phases of the disease. The rats were treated with SeNPs by intraperitoneal injection (0.5 mg SeNP/kg) for five consecutive days in the early phase (a day after injection of bleomycin) and late phase (a week after injection of bleomycin). The results showed that injection of SeNPs in the early phase improved the degree of alveolitis and inflammation and lung structure damage. Also, led to significant decreases in density of transforming growth factor- β1 (TGF-β1) in the lung and tumor necrosis factor-α (TNF-α) levels in the serum and lung homogenates compared with bleomycin-administrated group. Notably, treatment with the SeNP during the late phase did not show any ameliorative effects. Thus, the data suggest that SeNP has a protective effect against bleomycin-induced pulmonary injury in rats in the early phase of the disease. This might mean that SeNPs may be a new therapeutic agent for the improvement of this disease in the early phases.

Changes in inflammatory factors and protein expression in sulfur mustard (1LD50)-induced acute pulmonary injury in rats

• Animal model of SM was established by equal toxicity dose (1LD 50 )-induced acute pulmonary injury in rats using two methods. • Serum inflammatory factors and proteins in alveolar septa of the intraperitoneal SM group were increased. • The effects of SM may be related to its rapid absorption from the peritoneal cavity.

The effect of pulmonary injury in rats induced by paraquat

Objective: To study the effect of sodium aescinate on the development process of lung injury induced by paraquat. Methods: Forty-five health adult male SD rats were randomly divided into control group, PQ group, sodium aescinate group, and 15 rats in each group. The PQ group and sodium aescinate group were given a one-time intraperitoneal injection of 18mg/kg body weight of rats PQ, the control group was given the same amout normal saline. Rats in sodium aescinate group were injected 2 mg/kg body weight sodium aescinate into abdominal cavity for 7 days continually, but the same volume of saline was injected into the other groups. Finally, at 7, 14 and 28 days after PQ poisoning, five rats were kills for measuring lung tissue pathological changes and the value of TGF-β(1), TNF-α, hydroxyproline in each group. Results: The expression of TNF-α in serum of 7th day [ (17.03±0.82) ng/ml] and 14th day [ (15.74±0.91) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . The expression of TGF-β(1) in serum of 7th day[ (225.93±8.33) ng/ml], 14th day [ (216.62±9.48) ng/ml] and 28th[ (181.41±6.10) ng/ml] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . Lung tissue pathological changes showed, compared with control group, inflammatory injury at 7th day and fibrosis degree at 28th of rats' lung reduced on sodium aescinate group. The expression of hydroxyproline in rats' lung of 7th day[ (1.246±0.018) μg/mg], 14th day [ (1.269±0.034) μg/mg] and 28th[ (1.283±0.028) μg/mg] of sodium aescinate group were lower than the corresponding period of PQ groups', and the difference had statistical significance (P<0.05) . Conclusion: sodium aescinate could reduce the pulmonary inflammatory injury and hydroxyproline value of PQ poisoning rats, so sodium aescinate could ameliorate lung injury induced by PQ.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

BackgroundBone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism.MethodsAcute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 106/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung.ResultsNeurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression.ConclusionsThe grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

Impact of Olmesartan Medoxomil on Amiodarone-Induced Pulmonary Toxicity in Rats: Focus on Transforming Growth Factor-ß1.

Amiodarone (AD) is one of the most frequently prescribed anti-arrhythmic agents worldwide, but its effectiveness is limited due to the development of pulmonary toxicity. Several lines of evidence have suggested that AT1 receptor antagonists can attenuate pulmonary fibrosis in different animal models. This study was performed to evaluate the effect of olmesartan medoxomil (OM) on lung injury induced in rats by AD which was assessed biochemically (hydroxyproline content, MDA level and SOD activity), histologically (Ashcroft criteria and Masson's trichrome stain) and immunohistochemically (TGF-β1 expression in lung tissue). The expression levels of TGF-β1 and type I collagen mRNA were also determined by quantitative real-time polymerase chain reaction. Forty-eight adult male rats were randomized into six equal groups: control group, OM control groups, AD group received 40 mg/kg/day, p.o. for 4 weeks to induce pulmonary injury in rats and OM-treated groups received 0.6 and 6 mg/kg/day, p.o. concomitantly with AD for the same period. The results indicated that OM significantly decreased collagen deposition and hydroxyproline content, ameliorated pathological score and decreased the elevation in type I collagen and TGF-ß1 mRNA expression in lung tissue. Furthermore, it attenuated the AD-induced increase in the MDA level and increased SOD activity in lung tissue. It can be concluded that OM exerts a protective effect against AD-induced lung damage in rats which is attributed to modulation of pro-fibrogenic cytokine (TGF-β1) and antioxidant effect.

δV1-1 Reduces Pulmonary Ischemia Reperfusion-Induced Lung Injury by Inhibiting Necrosis and Mitochondrial Localization of PKCδ and p53

Ischemia-reperfusion (IR)-induced lung injury is one of the major contributing factors of morbidity and mortality after lung transplantation. To determine the IR-induced molecular changes in lung epithelial cells, we developed a cell-culture model that simulates lung preservation and transplantation. Six hours of cold ischemic time (CIT) and reperfusion elicited production of multiple inflammatory cytokines and chemokines and increased expression of endoplasmic reticulum (ER) proteins. Prolonged hypothermic condition (18 h CIT) reduced ER stress protein levels, and induced apoptosis and necrosis (via mechanisms related to mitochondrial permeability transition pore opening). Protein kinase C (PKCδ) was activated during CIT, and its downregulation via small interference (si) (in siRNA) RNA reduced IR-induced cytokine production and apoptotic cell death. δV1-1, a PKCδ peptide inhibitor, reduced translocation of PKCδ and p53 to the mitochondria after 18 h CIT, rescued ER stress protein expression, and converted the major mode of cell death from necrosis to apoptosis. Administration of δV1-1 effectively reduced lung transplantation and IR-induced pulmonary injury in rats. Therefore, inhibition of PKCδ by δV1-1 could be an effective strategy to ameliorate IR-induced lung injury by inhibiting the signaling pathways leading to necrosis.

Preliminary study on the biological effects of MiR-144 in pulmonary injury in rats induced by nanosized SiO₂

To Investigate the biological effects of miR-144 in rats' pulmanory injury induced by nanosized SiO₂preliminarily. 150 healthy SD rats were divided into five groups randomly: the control group, the nanosized SiO₂groups of 6.25, 12.5, 25.0 mg/ml, and the microsized SiO₂group of 25.0 mg/ml, 30 rats each group. Six rats were sacrificed for their pathological change on the 7th, 15th, 30th, 60th and 90th day after exposure. The expression levels of mature miR-144 in lung tissue of the rats after instilled intracheally nanosized SiO₂at 90d was detected by Quantitative Reverse Transcription PCR. Target prediction for miR-144 was conducted by databases of Target-scan, microRNA.org and miRDB. Function-significant enrichment analysis and signal pathway analysis for predicted target genes were respectively conducted by the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes, then target genes related to pulmonary fibrosis were screened out. The expression of miR-144 was up-regulated in lung tissue of rats exposed to nanosized SiO₂. The result was consistent with the results of high-throughput sequencing Hiseq 2000. The target genes of miR-144 related to fibrosis or signal pathway involved in fibrosis were screened out.They are SMAD4, SMAD5, ADAMTS3, ADAMTS15 and ADAMTS19. MiR-144 probably participate in the regulation of fibrosis, which may play an important role in pulmonary injury induced by nanosized SiO₂.

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

The major aim of this work was to study the protective effects of the cysteinyl-leukotriene antagonist montelukast (ML) and L-Carnitine (LC) against cyclophosphamide (CP)-induced pulmonary injury in experimental rats. Thirty adult male albino rats were categorized at random into five groups of 6 rats each. The first group served as normal control group. All other groups were injected once with CP (150 mg/kg, i.p.). The second group was kept as CP toxicity control group The third group was injected with ML (10 mg/kg/day, i.p.) once daily for 10 consecutive days before CP injection. The fourth group received LC (250 mg/kg/day, i.p.) once daily for 10 consecutive days before CP injection. The fifth group received ML plus LC once daily for 10 consecutive days before CP injection. The protective effects of these drugs were evaluated by assessment of lung glutathione reduced (GSH), thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione-S-transferase (GST), superoxide dismutase (SOD), and nitrite (NO2-) levels as oxidative and nitrosative stress biomarkers. This is in addition to assessment of serum levels of cyclooxygenase-II (COX-II) and lipooxygenase (LOX) as inflammatory parameters. Histopathological study was performed to confirm results of biochemical estimations. Pretreatment with ML, LC and their combinations effectively increased the levels of GSH and antioxidant enzyme GST and SOD in comparison with CP control rats Moreover, the serum activities of inflammatory enzymes COX-2 and LOX markedly decreased. In addition, ML, LC and their combinations effectively alleviated histopathological changes in lung tissue induced by CP. The results of this investigation show that ML, LC and their combination are true protective agents against CP-induced pulmonary injury in rats and may be promising for further clinical trials.

Protective effect of betaine against burn-induced pulmonary injury in rats.

This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.

Beclomethasone Dipropionate-Loaded Polymeric Nanocapsules: Development, In Vitro Cytotoxicity, and In Vivo Evaluation of Acute Lung Injury.

The aim of this work was to develop polymeric nanocapsules intended for the pulmonary delivery of beclomethasone dipropionate using ethyl cellulose or poly(ε-caprolactone). The formulations showed adequate physicochemical characteristics, namely, average diameter lower than 260 nm, low polydispersity index (< 0.2), negative zeta potential, neutral pH values, and encapsulation efficiencies close to 100%. The thermal analysis by DSC suggested that beclomethasone dipropionate encapsulated in the nanocapsules was in an amorphous state. In addition, both ethyl cellulose and poly(ε-caprolactone) nanocapsules were able to delay the drug photodegradation under UVC radiation. The in vitro drug release showed a prolonged release without burst effect using the dialysis bag diffusion technique. Moreover, ethyl cellulose and poly(ε-caprolactone) nanocapsules presented low in vitro cytotoxicity on 3T3 fibroblasts cells. In vivo, the formulations showed no acute pulmonary injury in rats. Therefore, the developed nanocapsules could be considered suitable carriers to be used for beclomethasone dipropionate pulmonary delivery.