Lung Tissue Malondialdehyde Levels Research Articles

Protective Role of Resveratrol Against Toluene-Induced Oxidative Stress in Rats

Toluene is a toxic substance commonly used in the industry that leads to oxidative stress in the body and causes in the formation of reactive oxygen species. In addition to the antioxidants produced by our body, we also obtain antioxidants through foods. Resveratrol is a polyphenol found in many plant species and possesses antioxidant properties. The effects of oxidative stress induced by toluene and the protective effect of resveratrol were investigated through changes in malondialdehyde (MDA) and glutathione (GSH) levels. Male rats were administered different doses of toluene and resveratrol (5 mg/kg, 10 mg/kg, 20 mg/kg), while control groups were given physiological saline and ethanol. At the end of the experiment, blood and lung tissues of the animals were examined, and MDA and GSH levels were measured. According to the obtained data, a significant increase in GSH activity was observed after the administration of toluene. However, in groups treated with combinations of toluene and various doses of resveratrol, a significant decrease in GSH levels was detected. While a significant increase in MDA levels in lung tissues was observed between the control groups and the toluene group, no significant change was observed in blood samples.

Codonopsis Radix Inhibits the Inflammatory Response and Oxidative Stress in Chronic Obstructive Pulmonary Disease Mice through Regulation of the Nrf2/NF-κB Signaling Pathway

Introduction: Chronic obstructive pulmonary disease (COPD) is a nonspecific chronic inflammatory lung disease with no known cure. Codonopsis Radix (CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR varieties on COPD mice. Methods: Sixty male-specified pathogen-free grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract combined with lipopolysaccharide, and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin, Masson, and periodic acid-Schiff stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an ELISA. Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking were used to predict signaling pathways, which were validated by Western blot analysis. Results: Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (p < 0.01). Western blot analysis also indicated significant downregulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant upregulation of Nrf2 protein expression in the lung tissues of mice treated with CR (p < 0.01). Conclusion: In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.

Evaluation of the Mitigation Effect of Spirulina Against Lung Injury Induced by Radiation in Rats.

Some compounds have been investigated to mitigate the effect of radiation on the lung, such as pneumonitis and fibrosis. This study aimed to examine the mitigation efficiency of Spirulina compared to the effect of Metformin. 25 male Wistar rats were allotted in five groups: control, Spirulina, Radiation, Radiation plus Spirulina, and Radiation plus Metformin. Rat chest regions were irradiated by 15 Gray (Gy) xradiation using aLINAC. Forty-eight hours after irradiation, treatment with Spirulina and Metformin began. Eighty days after irradiation, all rats were sacrificed, and their lung tissues were removed for histopathological, and biochemical assays. The results demonstrated that irradiation increased MDA (Malondialdehyde) levels while suppressing the SOD (superoxide dismutase) and GPx(glutathione peroxidase) activity in the irradiated group. MDA levels in lung tissues were reduced with Metformin but not with Spirulina. Both Metformin and Spirulina increased the SOD and GPx activity in lung tissue. Moreover, histopathological evaluations showed extensive changes in the lung tissue including infiltration of lymph cells around the bronchioles and blood vessels, thickening of the alveolar wall, and the disruption of the alveolar structure, as well as accumulation of collagen fibers. Administration of Spirulina and Metformin significantly reduced pathological changes in lung tissue, although the effect of Metformin was greater than that of Spirulina. Spirulina could mitigate radiation-induced lung injury moderately, although Metformin is more effective than Spirulina as a mitigator agent.

Reducing effects of ginkgo biloba (egb761) extract on skeletal muscle ischemia-reperfusion injury in rats

Aim: The restoration of circulation following a period of ischemia results in the release of the metabolites that accumulate in the ischemic tissue into circulation with untoward effects on the organs. Many studies have been conducted to date into the prevention of such ischemia-reperfusion injuries. Ginkgo Biloba extract is known to have antioxidant effects, although there is a lack of data on its effects on a skeletal muscle ischemia-reperfusion model. The present study investigates the use of Ginkgo biloba extract (egb761) for the reduction of experimentally-induced skeletal muscle ischemia-reperfusion injury. Material and Methods: A total of 32 Sprague-Dawley rats were divided into four groups as follows: Group 1 (n=8), control group; Group 2 (n=8), limb ischemia model; Group 3 (n=8), ischemia-reperfusion model; and Group 4 (n=8), Ginkgo biloba group. After the models were created in each group, soleus muscle, lung and liver tissues were removed. Tissue malondialdehyde (MDA) levels were measured biochemically to demonstrate lipid peroxidation. The percentage of viable cells in the soleus muscle was calculated through a histochemical examination. Results: The comparison of soleus muscle MDA levels revealed no statistically significant difference between Group 1 and Groups 2 and 3, whereas the levels were significantly lower in Group 1 than those in Group 4 (p&lt;0.05). Similarly, there was a significant reduction in Group 4 than in Group 3 (p&lt;0.05). The analysis of lung tissue MDA levels revealed no significant difference between Group 1 and Group 2, whereas MDA levels were significantly increased in Group 3 than in Group 1 (p&lt;0.05), while there was no difference between Group 1 and Group 4. The analysis of liver tissue MDA levels showed significantly increased levels in Groups 3 and 4 than in Group 1 (p&lt;0.05). The percentage of viable cells was significantly decreased in Groups 2 and 3 than in Group 1 (p&lt;0.05). There was a significant reduction in Group 4 than in the control group. Conclusion: The results of the present study suggest that Ginkgo biloba (EGb761) extract may be used to reduce the local and systemic effects occurring after the restoration of blood flow following acute arterial occlusion. There is, however, an apparent need for large-scale, prospective, randomized trials to demonstrate the efficacy of Ginkgo biloba treatment.

Inhibiting the ROCK Pathway Ameliorates Acute Lung Injury in Mice following Myocardial Ischemia/reperfusion

ABSTRACT To clarify the role of Y-27632, a selective inhibitor of Rho-associated coiled-coil forming protein kinase (ROCK), in acute lung injury (ALI) induced by myocardial ischemia/reperfusion (I/R). Mice were randomized into Sham, I/R, and Y-27632 (10, 20 or 30 mg/kg) + I/R groups, and hemodynamics, infarcted area, the protein concentration, neutrophils in bronchoalveolar lavage fluid (BALF), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were assessed. Pathological changes were evaluated by hematoxylin-eosin (HE) staining; protein and gene expression were measured by Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR); and apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. ROCK1 and ROCK2 expression was up-regulated in lung tissues of I/R mice compared to sham mice. Y-27632 decreased the protein concentration and the neutrophils in BALF in I/R mice, improved hemodynamics and reduced infarct size (IS)/area at risk (AAR) ratio. In addition, pathological changes in lung tissues of Y-27632-treated mice were mitigated, and these alterations were accompanied by decreases in MDA levels in lung tissues and increases in SOD and GSH-Px levels. Moreover, in I/R group, the number of apoptotic cells in lung tissue was higher than that in sham group, and p53, Caspase-3 and Bax expression was up-regulated; however, following treatment with Y-27632 (10, 20 and 30 mg/kg), these changes were reversed. Inhibition of ROCK pathway by Y-27632 ameliorated ALI in myocardial I/R mice by mitigating oxidative stress, inflammation and cell apoptosis.

Effect of asiaticoside on hyperoxia-induced bronchopulmonary dysplasia in neonatal rats and related mechanism

To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.

Mesenchymal stem cells alleviate hydrochloric acid-induced lung injury through suppression of inflammation, oxidative stress and apoptosis in comparison to moxifloxacin and sildenafil

IntroductionAcute lung injury (ALI) is a severe life-threatening disease causing uncontrolled pulmonary inflammation and oxidative damage. There are still no effective therapies for this disease. The aim of this study was to evaluate the protective role of mesenchymal stem cells, moxifloxacin, sildenafil or a combination of moxifloxacin and sildenafil against hydrochloric Acid (HCl) - induced ALI. MethodsHCl or saline was injected intra-tracheally and after 2 h, moxifloxacin, sildenafil, moxifloxacin + sildenafil or mesenchymal stem cells were injected. After 7 days, rats were sacrificed for evaluation of the blood chemistry and inflammation via determination of the level of oxidative stress markers, apoptosis and the histopathological alterations by H&E. ResultsIn HCl-injected rats, there were a significant increase in total white blood cells (WBCs), lymphocytes, malondialdehyde (MDA) and caspase-3 gene expression. Also, there were a significant decrease in superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and Hemeoxygenase-1 (HO-1) gene expression in lung tissue. On the other hand, treatment of lung injured rats with mesenchymal stem cell, moxifloxacin, sildenafil or a combination of moxifloxacin and sildenafil showed a significant decrease in WBCs and lymphocytes and ameliorated the histopathological changes. MDA level in lung tissue was only significantly lowered in rats treated with moxifloxacin alone or in combination with sildenafil or MSCs. GSH was just increased in rats treated with moxifloxacin, sildenafil or with MSCs. Antioxidant parameters and gene expression of HO-1 and caspase-3 were significantly modulated in rats treated with MSCs. ConclusionMSCs ameliorated the toxic effects of HCl through their ability to decrease inflammation, oxidative stress, and apoptosis in acute lung injury.

Methylene Blue Attenuates Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats.

Objective This study was aimed to investigate the protective effect of methylene blue against lung injury induced by reperfusion of ischemic hindlimb in a rat model. Methods Twenty-four healthy adult male Sprague-Dawley rats were equally randomized into three groups: sham (SM) group, ischemia reperfusion (IR) group, and methylene blue (MB) group. Rats in both IR and MB groups were subjected to 4 h of ischemia by clamping the left femoral artery and then followed by 4 h of reperfusion. Treatment with 1% methylene blue (50 mg/kg) was administrated intraperitoneally at 10 min prior to reperfusion in the MB group. After 4 h of reperfusion, malondialdehyde (MDA) level, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities in lung tissue were detected; inflammatory cytokines, including IL-1β and IL-6, were measured in bronchoalveolar lavage fluid (BALF); correspondingly, the morphological changes and water content in both gastrocnemius muscle and lung samples were evaluated. Results Hindlimb IR caused remarkable morphological abnormalities and edema in both muscle and lung tissues. SOD activity was decreased, both the MPO activity and MDA level in lung tissue, as well as IL-1β and IL-6 levels in BALF, were increased in the IR group (p < 0.05). Compared with the IR group, SOD activity was increased, whereas MPO activity and MDA level in lung tissue and IL-1β and IL-6 levels in BALF were decreased in the MB group (p < 0.05). Also, the histological damage and edema in both lung and muscle tissues were significantly attenuated by the treatment of methylene blue. Conclusion Methylene blue attenuates lung injury induced by hindlimb IR in rats, at least in part, by inhibiting oxidative stress.

Does Urinary Trypsin Inhibitor Have a Role in Acute Lung Injury Induced by Pulmonary Contusion

We evaluate the efficacy of urinary trypsin inhibitor (UTI) on inflammation, oxidative stress, hypoxemia, and diseased lesion in a rat model of acute lung injury induced by blunt trauma. Rats were allocated to 4 groups. One group served as normal control. The other 3 groups had a moderate pulmonary contusion. Except for 1 sham group administrated saline, 1 group was administrated low-dose UTI (20,000 U/kg), and another group was administrated high-dose UTI (50,000 U/kg). Twelve hours after contusion, neutrophil counting in bronchoalveolar lavage fluid (BALF) was performed and tumor necrosis factor α level and albumin level in BALF was tested. Lung tissue malondialdehyde levels, superoxide dismutase, and catalase activity was investigated, and blood gas analysis and contusion volume quantification using 3-dimensional computed tomography were performed. High-dose UTI significantly decreased neutrophil count and tumor necrosis factor α level in BALF (P<0.05) and decreased albumin level in BALF but without significance. Lung tissue malondialdehyde levels was significantly reduced, whereas superoxide dismutase and catalase activity were elevated by UTI with significance (P<0.05) especially high-dose UTI. No statistical significance was seen in the change in arterial oxygen partial pressure (PaO2) and contusion volume by UTI (P>0.05). UTI has a dose-dependent trend to ameliorate inflammatory and oxygen stress in pulmonary contusion-induced acute lung injury. However, the effect on hypoxemia and contusion lesion and the best administration regime should be investigated in future study.

Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis

Sepsis and septic shock are are among the major causes of mortality in intensive care units. The lung and kidney are the organs most affected by sepsis. Evidence exists that lipid peroxidation and apoptosis may be responsible for the high mortality due to sepsis. Ischemic preconditioning (IP) is a method for the protection of tissues and organs against ischemia/reperfusion injury by reducing reactive oxygen species levels, lipid peroxidation and apoptosis. In the present study, the effects of IP were investigated in cecal ligation and puncture (CLP)-induced sepsis in rats. The three groups of animals used in the present controlled study were the sham-operated group (sham, n=7), which only underwent a laparotomy; the sepsis group (sepsis, n=7), which underwent cecal ligation and perforation; and the IP + sepsis group (IP+sepsis, n=7), which underwent CLP immediately prior to the application of three cycles of IP to the hind limb. The study was terminated at 6 h after the induction of CLP. Blood, kidney and lung tissue samples were collected for the determination of serum creatinine, blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL) and lung tissue malondialdehyde (MDA) levels, as well as histological examination. The serum creatinine, plasma NGAL and lung tissue MDA levels in the sepsis group were significantly increased compared with those in the sham and the IP+sepsis groups (P<0.05). Alveolar macrophage counts, histological kidney and lung injury scores, kidney (caspase 3) and lung tissue immuonreactivity (M30) scores in the sepsis group were also significantly increased compared with those in the sham and IP+sepsis groups (P<0.05). The alveolar macrophage count in the IP+sepsis group was increased compared with that in the sham group (P<0.05). In conclusion, IP inhibits lipid peroxidation and attenuates histological injury and apoptosis in the lung and kidney during sepsis.

Diagnostic value of ischaemia-modified albumin in pulmonary contusion in rats

BackgroundPatients with pulmonary contusion (PC) are at increased risk of development of complications and death after trauma. The early diagnosis and determination of severity of PC could improve clinical outcomes. The aim of the study was to determine the diagnostic value of ischaemia-modified albumin (IMA) in a PC model in rats. MethodsThirty-two Sprague-Dawley rats were randomly allocated to four groups; the uninjured control Group I (n=7) and the uninjured control Group II (n=7) were euthanised at 2 and 6h, respectively, and PC groups III (n=9) and IV (n=9) were euthanised at 2 and 6h after trauma, respectively. The serum level of IMA, tissue and serum malondialdehyde (MDA) levels, and histopathological damage scores of the lung tissue were determined. ResultsSerum IMA and lung tissue MDA levels in the PC groups were not significantly different to those of the control groups (p=0.555; p=0.086, respectively). Serum MDA levels were significantly higher in the PC groups than in the control groups (p=0.011). When histopathological changes in lung parenchyma were evaluated, there was a statistical difference between the injured and uninjured groups for inflammation and lung injury (p=0.017; p=0.001, respectively). However, there was no significant correlation between the histopathological score and biochemical parameters. ConclusionOur preliminary findings suggest that there is no significant change of serum IMA levels in the acute phase of PC induced by blunt chest trauma.

Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway*

To examine whether niacin attenuates lung inflammation and improves survival during sepsis and to determine whether the beneficial effects of niacin are associated with downregulation of the nuclear factor (NF)-κB pathway. Prospective laboratory study. University laboratory. Male Sprague-Dawley rats (n = 119). To induce endotoxemia in rats, lipopolysaccharide (Escherichia coli, O26:B6) at a dosage of 10 mg/kg was injected into a tail vein and 10 mins later, vehicle, a low dose of niacin (360 mg/kg), or a high dose of niacin (1180 mg/kg) was administered once through an orogastric tube, respectively. We observed the survival of the subjects for 72 hrs. At 6 hrs postlipopolysaccharide, we euthanized animals and measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, tumor necrosis factor-α, and interleukin-6 gene expressions and histologic damages in lung tissues. We also measured nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, and malondialdehyde levels in lung tissues. High dose of niacin suppressed NF-κB activation and proinflammatory cytokine gene expressions in lung tissues, reduced histologic lung damages, and improved survival in endotoxemic rats. Furthermore, it increased nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and glutathione levels and decreased malondialdehyde level in lung tissues. High dose of niacin attenuated lung inflammation, reduced histologic lung damages, and improved survival during sepsis in rats. These therapeutic benefits were associated with downregulation of the NF-κB pathway.

Responses of Broilers under Cold Conditioning (15ºC) to Dietary Triiodothyronine and Iodine Combined to Antioxidants (Selenium and Vitamin C)

Summary This experiment was conducted to determine the influence of dietary antioxidants (selenium (Se) and vitamin C), and triiodothyronine (T3) to iodine on biochemical parameters, malondialdehyde (MDA), catalase (CAT) in broilers exposed cold. In the study, 150, one-day-old, broiler chicks (Ross 308) were used. Chicks were randomized into 1 control and 4 treated groups each containing 30 birds and each experimental group comprised 3 replicates of 10 birds. The experimental groups were as follow: control was fed with basal diet; group I was fed with basal diet supplemented with 1 mg/kg selenium as sodium selenite plus 2 mg/kg iodine as calcium iodate; group II was fed with basal diet supplemented 1 mg/kg selenium plus 1 mg/kg T3; group III was fed with basal diet supplemented with 250 mg/kg vitamin C as ascorbic acid plus 1 mg/kg iodine; group IV was fed with basal diet supplemented with 250 mg/kg vitamin C plus 1 mg/kg T3. Plasma T3, triglyceride and SGPT were significantly different among the groups. MDA level in heart tissue of control group was found significantly higher than those of other groups (P<0.01). MDA levels in liver (P<0.01) and abdominal fat (P<0.001) tissues of control and group I were determined significantly higher than those of other groups, whereas MDA level in lung tissue was similar found in all groups. The CAT activity of liver of control and group I was found significantly the highest (P<0.001). Results showed that cold exposure in broilers induced oxidative damage in tissues, but this damage decreased partly in supplement groups, except group I.

Mild Hypothermia Improves Survival During Hemorrhagic Shock Without Affecting Bacterial Translocation

Background: Accidental hypothermia in patients with hemorrhagic shock (HS) is associated with increased mortality. However, experimental mild and moderate hypothermia has beneficial effects. The mechanisms for beneficial effects of hypothermia have not been completely understood. Therefore, the aim of this study was to investigate the effect of hypothermia on survival, bacterial translocation (BT), and remote pulmonary injury in a controlled HS model in rats. Methods: HS was achieved by blood withdrawal through femoral vein. Rats in the normothermia group (group I) were maintained at 37°C. Mild hypothermia group (group II) was observed at 32°C that was spontaneously induced by exposure to ambient temperature. Moderate hypothermia of 28°C was actively induced by external cooling in group III for 90 min. Survival and neurological deficit scores (NDS) were recorded at 24th hr. Mesenteric lymph nodes, liver and spleen samples were collected. Myeloperoxidase (MPO) and malondialdehyde (MDA) levels were measured in lung tissue. Results: Blood pressure significantly increased in hypothermia groups. Mild hypothermia significantly increased survival. No difference was found in BT rates in groups. Hypothermia was found to significantly decrease the NDS points in group III, compared to group I. There was no difference in lung tissue MPO levels among groups. Lung tissue MDA levels increased significantly in groups II and III. Conclusions: Mild hypothermia improved blood pressure, survival, and neurological outcome with a possible detrimental effect on pulmonary ROS production during HS in rats. These effects of hypothermia are not associated with BT.

Hyperoxygenated Solution Preconditioning Attenuates Lung Injury Induced by Intestinal Ischemia Reperfusion in Rabbits

The current study was undertaken to elucidate the possible therapeutic effects of hyperoxygenated solution (HOS) preconditioning on lung injury induced by intestinal ischemia/reperfusion (I/R) in rabbits. Eighty rabbits were randomly divided into four groups (n = 20 each) as follows: (1) control group in which sham operation was performed (sham group), (2) HOS pretreatment group and sham operation (HOS + sham group), (3) ischemia/reperfusion group (I/R group), (4) HOS pretreatment and ischemia/reperfusion group (HOS + I/R group). Intestinal I/R model was produced by clamping superior mesenteric artery with an atraumatic vascular clamp for 1 h, and followed by reperfusion for 2 h. Animals in HOS + sham group and HOS + I/R group received intravenous HOS infusion (20 mL/kg, 10 mL/kg.h for 2 h) every day for 5 d before operation, and animals in sham group and I/R group received the same amount of normal saline in the same way. At the end of reperfusion, 8 animals from every group were sacrificed and histopathological changes of lung were observed; pulmonary edema, lung myeloperoxidase activity, superoxide dismutase activity, and malondialdehyde levels in lung tissues were also detected. The rest 12 animals in every group underwent 60 min of intestinal ischemia followed by 72 h of reperfusion, and effects of HOS pretreatment on survival in rabbits with lung injury induced by intestinal I/R was observed. When rabbits were subjected to 60 min of intestinal ischemia, a high incidence of mortality was observed within 24 h. In this situation, HOS preconditioning before the start of ischemia/reperfusion significantly reduced the mortality. HOS preconditioning also decreased lung wet/dry ratio, neutrophil infiltration, lipid membrane peroxidation, and increased superoxide dismutase activity in the lungs after intestinal I/R compared with the I/R-treated rabbit lungs without HOS treatment. Histopathological analysis also indicated the effectiveness of HOS pretreatment. HOS preconditioning could preserve superoxide dismutase activity, decrease lipid membrane peroxidation and neutrophil infiltration in the lungs, then ameliorate the deleterious changes in pulmonary injury induced by intestinal I/R.

Melatonin alleviates lung damage induced by the chemical warfare agent nitrogen mustard

The cytotoxic mechanism of mustards has not been fully elucidated; recently, we reported that reactive oxygen species, nitric oxide [produced by inducible nitric oxide synthase (iNOS)] and peroxynitrite are involved in the pathogenesis and responsible for mustard-induced toxicity. Melatonin, a potent antioxidant molecule, acts as an iNOS inhibitor and a peroxynitrite scavenger. Using the prototypic nitrogen mustard (mechlorethamine/HN2) as a model and based on its known cytotoxic mechanisms, the present study was performed to test melatonin for its capability in protecting the lungs of injured male Wistar rats. Lung mustard toxicity was induced via an intratracheally injection of HN2 (0.5 mg/kg) dissolved in saline (100 μl). Control animals were injected the same amount of saline only. Melatonin was administered intraperitoneally with two different doses (20 mg/kg or 40 mg/kg) beginning 1 h before HN2 application and continued every 12 h for six replications. Forty-eight hours after the last melatonin injection, the animals were sacrificed and their lungs were taken for further assay, i.e., malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPx) and iNOS activity. Additionally their urine was collected for nitrite–nitrate (NO x ) analysis. HN2 injection caused increased iNOS activity and MDA levels in lung tissue and NO x values in urine; lung GPx activity was significantly depressed. Melatonin restored all of these oxidative and nitrosative stress markers in a dose-dependent manner. In conclusion, the results of study provide evidence that melatonin may have the ability to reduce mustard-induced toxicity in the lungs.

Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

To investigate the effect of exogenous erythro-poietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate- induced acute necrotizing pancreatitis (ANP). Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-alpha, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored. The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-alpha (TNF-alpha) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h. EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI.

Pretreatment with Simvastatin Reduces Lung Injury Related to Intestinal Ischemia-Reperfusion in Rats

In this rat model study we evaluated whether pretreatment with simvastatin affects the severity of acute lung injury caused by intestinal ischemia-reperfusion (I/R). Twenty-four animals were randomly allocated to three equal groups (sham, control, simvastatin). The simvastatin group was pretreated with simvastatin 10 mg x kg(-1) x day(-1) for 3 days, whereas the other groups received placebo. The simvastatin and control groups underwent 60 min of superior mesenteric artery occlusion and 90 min of reperfusion. Compared with the simvastatin group, the control group exhibited significantly more severe intestinal I/R-induced acute lung injury, as indicated by lower Pao2 and oxygen saturation (P = 0.01 and P = 0.005, respectively) and higher mean values for neutrophil infiltration of the lungs (P = 0.003), total lung histopathologic injury score (P = 0.003), lung wet-to-dry weight ratio (P = 0.009), and lung-tissue malondialdehyde levels (P = 0.016). The control and simvastatin groups had similar serum levels and similar bronchoalveolar lavage fluid levels of cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and P-selectin at all measurements, except for a significantly higher level of bronchoalveolar lavage fluid P-selectin in the control group (P = 0.006). Pretreatment with simvastatin reduces the severity of acute lung injury induced by intestinal I/R in rats.

CARDIAC RELEASE OF B-TYPE NATRIURETIC PEPTIDE, CYTOKINES, AND INFLAMMATORY MARKERS IN CONGENITAL HEART DISEASE: PERIOPERATIVE SETTING UNDERGOING CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS

In this study, we determined the effects of various body temperatures (BTs) after initiation of lipopolysaccharide (LPS)-induced lung injury.Forty-nine, adult, male, Sprague-Dawley rats each weighing 300 to 400 g were usedThe treated rats were challenged with intraperitoneal (IP) administration of 5 mg/kg LPS. Control animals received IP saline solution injections. After 16 h, treated and control animals were anesthetized. The animals received direct intratracheal (IT) injection of LPS (1 mg/0.2 mL) or saline solution (control animals). A cooling or heating blanket was then used to control BT. The rats were randomly assigned to three control groups of mild hypothermia (34 degrees C) plus saline solution, normothermia (37 degrees C) plus saline solution, and mild hyperthermia (39 degrees C) plus saline solution, and three LPS groups of mild hypothermia plus LPS, normothermia plus LPS, and mild hyperthermia plus LPS, where each condition was maintained for 5 h. The mean arterial pressure (MAP) and blood gas concentrations were measured. BAL was done in the left lung 5 h after the IT injection of LPS with temperature control. Parts of the right lung were excised for myeloperoxidase (MPO) and malondialdehyde (MDA) measurements, whereas the rest was collected for wet/dry (W/D) ratio determination.Normothermia plus LPS caused significantly increased W/D ratio, LDH activities, protein concentrations, and tumor necrosis factor-alpha concentrations in BAL fluid, and MPO activities and MDA levels in lung tissues when compared to saline solution control group. MAP and Pao(2) were significantly decreased. The pathologic picture also showed increased neutrophil infiltration in lung tissues. In contrast, treatment with mild hypothermia but not hyperthermia significantly attenuated these parameters when compared with the normothermia-plus-LPS group.These experimental data suggest that mild hypothermia applied after initiation of acute lung injury induced by LPS in rats had a protective effect by inhibiting the inflammatory reaction.

Effects of Various Body Temperatures After Lipopolysaccharide-Induced Lung Injury in Rats

Study objectives In this study, we determined the effects of various body temperatures (BTs) after initiation of lipopolysaccharide (LPS)-induced lung injury. Design and setting Forty-nine, adult, male, Sprague-Dawley rats each weighing 300 to 400 g were used Methods The treated rats were challenged with intraperitoneal (IP) administration of 5 mg/kg LPS. Control animals received IP saline solution injections. After 16 h, treated and control animals were anesthetized. The animals received direct intratracheal (IT) injection of LPS (1 mg/0.2 mL) or saline solution (control animals). A cooling or heating blanket was then used to control BT. The rats were randomly assigned to three control groups of mild hypothermia (34°C) plus saline solution, normothermia (37°C) plus saline solution, and mild hyperthermia (39°C) plus saline solution, and three LPS groups of mild hypothermia plus LPS, normothermia plus LPS, and mild hyperthermia plus LPS, where each condition was maintained for 5 h. The mean arterial pressure (MAP) and blood gas concentrations were measured. BAL was done in the left lung 5 h after the IT injection of LPS with temperature control. Parts of the right lung were excised for myeloperoxidase (MPO) and malondialdehyde (MDA) measurements, whereas the rest was collected for wet/dry (W/D) ratio determination. Results Normothermia plus LPS caused significantly increased W/D ratio, LDH activities, protein concentrations, and tumor necrosis factor-α concentrations in BAL fluid, and MPO activities and MDA levels in lung tissues when compared to saline solution control group. MAP and Pa o 2 were significantly decreased. The pathologic picture also showed increased neutrophil infiltration in lung tissues. In contrast, treatment with mild hypothermia but not hyperthermia significantly attenuated these parameters when compared with the normothermia-plus-LPS group. Conclusions These experimental data suggest that mild hypothermia applied after initiation of acute lung injury induced by LPS in rats had a protective effect by inhibiting the inflammatory reaction.