Lung Malondialdehyde Research Articles

Beneficial Effect of Etanercept on Hyperoxic Lung Injury Model in Neonatal Rats

ABSTRACTPurpose: To determine whether prophylaxis with etanercept, an anti-inflammatory drug, would decrease the severity of lung injury in a neonatal rat model of bronchopulmonary dysplasia (BPD); Materials and Methods: Rat pups were divided into three groups: pups exposed to room air (group 1; n = 10), to hyperoxia + placebo (group 2; n = 9), and to hyperoxia + etanercept (group 3; n = 8). Lung morphology was assessed by alveolar surface area percentage, which is a measure of alveolar size. The severities of lung inflammation and antioxidant capacity were assessed by quantifying tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), malondialdehyde (MDA), and superoxide dismutase (SOD) from lung homogenate; Results: The percentage of alveolar surface areas were significantly higher in group 3 compared to group 2 (p = .004) and similar in both group 1 and group 3 (p = .21). The mean level of lung MDA was significantly higher in group 2 compared to group 1 and group 3 (p < .05 for both). Lung homogenate SOD activities in group 3 was significantly higher than group 2 (p < .001). Furthermore, group 3 pups had lower levels of TNF-α and TGF-β in lung homogenate than that in group 2 (p < .05 for both) but similar in both group 1 and group 3; Conclusion: Etanercept has favorable effects on alveolarization as well as inflammation and oxidative stress markers in a neonatal rat model of BPD.

The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down-regulation of the reactive oxygen species-dependent nuclear factor κB pathway.

The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor κB (NF-κB) pathway in hemorrhagic shock (HS) rats. HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor κB-α and inhibitor κB-α expressions, nuclear NF-κB p65 expression, NF-κB p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-α, IL-6, and IL-8 levels in the serum. The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione-glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-κB pathway; suppressed TNF-α, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage. A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species-dependent NF-κB pathway.

Concomitant exposure to cigarette smoke and coal dust induces lung oxidative stress and decreases serum MUC5AC levels in male rats

This study aimed to investigate whether concomitant exposure to cigarette smoke and coal dust could activate the epidermal growth factor receptor (EGFR) for MUC5AC expression. Thirty-two male Wistar rats were divided into the following groups (n = 8 each): control group (C); exposed to cigarette smoke plus coal dust at doses of 6.25 mg/m3 (CS + CD1); 12.5 mg/m3 (CS + CD2); and 25 mg/m3 (CS + CD3). The duration of exposure was 21 days, 1 hour/day. Lung malondialdehyde level was analyzed colorimetrically. Serum EGF and MUC5AC expression were measured by ELISA. Expression of lung EGFR and MUC5AC were measured by a confocal laser scanning microscopy. The level of lung malondialdehyde was higher significantly in all doses of exposure compared with control group (p < 0.05). The level of serum EGF was significantly increased in CS + CD2 group compared with control group or CS + CD1 group. The expression of EGFR was not significantly different among all the treatment groups (p > 0.05). Serum MUC5AC levels were significantly lower in the two highest doses of coal dust compared with the control group. In conclusion, subchronic combined exposure to cigarette smoke and coal dust induces lung oxidative stress and inflammation and decreases serum MUC5AC level.

Hypoxia-induced acute lung injury is aggravated in Streptozotocin diabetic mice

ABSTRACTPurpose: Hypoxia is an inevitable consequence of many respiratory diseases resulting from inadequate alveolar ventilation. As pulmonary dysfunction is recently recognized as one of the many clinical features associated with diabetes, this study aims to investigate the effect of streptozotocin (STZ)-induced diabetes on hypoxia-induced lung injury. Materials and Methods: Mice were randomly allocated to four groups (Control, Hypoxia, Diabetes, Diabetes+Hypoxia). Control and type I diabetic (100 mg/kg STZ-treated) mice were followed for 4 weeks and finally exposed to normoxia or hypoxia (8% O2). Twelve hours later, lung tissues were collected for histopathologic examination, and determination of interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, and Toll-like receptor (TLR)4 expression. Results: STZ-induced diabetes aggravated histopathological changes in the lung exposed to acute hypoxia. Hypoxia increased lung MDA level but decreased T-AOC and SOD activity. STZ-induced diabetic mice presented significant increases in MDA level and SOD activity in the lung. Moreover, no difference was found in the levels of both oxidant index (MDA) and anti-oxidant indexes (T-AOC and SOD) between “Hypoxia” group and “Hypoxia plus Diabetes” group. On the other hand, STZ-induced diabetic mice presented significant increases in pulmonary neutrophil infiltration, pro-inflammatory cytokines (IL-1β and IL-6) production, as well as TLR4 expression. Although acute hypoxia alone had no significant effect on pulmonary inflammatory markers, it profoundly increased STZ-diabetes-induced neutrophil infiltration, pro-inflammatory cytokine production, and TLR4 expression in lung tissues. Conclusions: STZ-induced diabetes may aggravate acute hypoxia-induced lung injury through enhancing pulmonary inflammatory responses.

Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and transforming growth factor -β/Smad signaling pathway

To investigate whether heparin has a beneficial effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats, and to explore the possible underlying mechanisms. Thirty-two adult Sprague-Dawley (SD) rats were randomly assigned into the control, heparin control, model, and heparin treatment groups, with 8 in each group. ALI rat model was reproduced by intratracheal instillation of LPS at a dose of 1 mg/kg. The rats in the control and heparin control groups received an equal volume of normal saline at the same times. The rats in the heparin control and heparin treatment groups were intravenously received 50 U/kg heparin every 1 hour after the induction of ALI. Animals were sacrificed 24 hours after LPS challenge. Bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Histopathological evaluation, lung wet/dry (W/D) ratio, malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of inflammatory factor in BALF. Expression of inducible nitric oxide synthase (iNOS) mRNA in the lung of rats was measured by reverse transcription-polymerase chain reaction (RT-PCR). Western Blot was used to determine the expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad in the lung tissues. The expression of iNOS in lung was determined by immunohistochemistry. In the control and heparin control groups, lung tissue showed a normal structure and clear pulmonary alveoli under a light microscope. In the model group, ALI characters such as extensive thickening of the alveolar wall, significant infiltration of inflammatory cells, demolished structure of pulmonary alveoli, and hemorrhage were found. In the heparin treatment group, heparin treatment markedly alleviated LPS-induced these pathological changes in lung. Compared with control and heparin control groups, lung W/D ratio, lung MDA, NO and MPO levels, and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF in the model group were increased significantly. Compared with the model group, lung W/D ratio, lung MDA, NO and MPO levels, and TNF-α and IL-6 in BALF in the heparin treatment group were significantly decreased [W/D ratio: 7.54 ± 0.17 vs. 10.69 ± 0.15,MDA (mmol/mg): 2.01 ± 0.30 vs. 2.51 ± 0.25, NO (μmol/L): 3.07 ± 0.21 vs. 3.89 ±0.14,MPO (U/g): 1.94 ± 0.09 vs. 2.74 ± 0.20, TNF-α (μg/L): 201.80 ± 0.27 vs. 297.53 ± 0.34,IL-6 (μg/L): 38.41 ± 0.25 vs. 46.31 ± 0.31,all P<0.05]. RT-PCR showed that the expression of iNOS mRNA in the heparin treatment group was significantly lower than that in the model group (2 (-Δ ΔCt): 3.04 ± 0.18 vs. 4.37 ± 0.15, P < 0.05). Western Blot showed that compared with control group, the protein expressions of iNOS and TGF-β1, and phosphorylation of Smad2 and Smad3 were significantly increased, and the heparin could inhibit the protein expressions compared with model group. Immunohistochemistry showed that positive expressions of iNOS in alveolar epithelial cell and capillary endothelial cell in the heparin treatment group were significantly lower than those in the model group. Heparin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of nitric oxide synthase expression and the TGF-β/Smad pathway.

Effects of lettuce glycoside B in ameliorating pulmonary fibrosis induced by irradiation exposure and its anti-oxidative stress mechanism.

The present research assessed the effects of lettuce glycoside B (LGB), a compound separated and purified from Pterocypsela laciniata, on irradiation-induced pulmonary fibrosis and explored the mechanism involved. Animal model of irradiation exposure inducing pulmonary fibrosis was established by Co irradiator. Rats were intraperitoneally treated with LGB (100, 200 and 400mg/kg) once per day for a month. Lung index data were analyzed. The levels of fibrosis were assessed by hydroxyproline (Hyp) of pulmonary and lung tissue sections after irradiation exposure. Alveolitis and fibrosis levels were calculated from semi-quantitative analysis of hematoxylin and eosin and Masson's trichrome lung section staining. The serum levels of transforming growth factor β1 (TGF-β1), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) were also evaluated. Antioxidant enzymes of superoxide dismutase (SOD) were measured in serum. Moreover, we also measured serum malondialdehyde (MDA) levels, a marker of oxidative stress. Treatment with LGB significantly reduced mortality rates and lung index scores and MDA content, enhanced SOD and other antioxidant enzymes activity, and regulated serum levels of TGF-β1, IL-6, and TNF-α. These results demonstrated that LGB significantly inhibited irradiation-induced pulmonary fibrosis. Furthermore, the results suggested promising clinical effect of LGB therapies for treating irradiation-induced pulmonary fibrosis.

Ulinastatin prevents acute lung injury led by liver transplantation

BackgroundLittle is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism. Materials and methodsRats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed. ResultsAccording to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1β, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1β, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1β, IL-6, and MDA levels and SOD activity. ConclusionsUTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.

Effects of sphingosylphosphorylcholine against oxidative stress and acute lung ınjury ınduced by pulmonary contusion in rats

Background/purposeThe goal of this study was to evaluate effects of exogenous sphingosylphosphorylcholine (SPC) administration on acute lung injury induced by pulmonary contusion in rats. MethodsEight animals were included in each of the following five groups: control, contusion, contusion phosphate-buffered solution (PBS), contusion SPC 2, contusion SPC 10. SPC was administered 3days at a daily two different doses of 2μm/ml and 10μm/ml intraperitoneally. The severity of lung injury was determined by the neutrophil activation and histological and immunohistochemical changes in the lung. Malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) were determined to evaluate the oxidative status in the lung tissue. ResultsTreatment with 2μM SPC inhibited the increase in lung MDA and NO levels significantly and also attenuated the depletion of SOD, GPx, and GSH in the lung injury induced by pulmonary contusion. These data were supported by histopathological findings. The inducible nitric oxide synthase (iNOS) positive cells and apoptotic cells in the lung tissue were observed to be reduced with the 2μM SPC treatment. But, the 10μM SPC treatment did not provide similar effects. ConclusionsIn conclusion, these findings suggested that 2μM SPC can attenuate lung damage in pulmonary contusion by prevention of oxidative stress, inflammatory process and apoptosis. All these findings suggest that low dose SPC may be a promising new therapeutic agent for acute lung injury.

The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity.

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1β (TGF-1β) levels were significantly higher than the sham group (in all, p < 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1β levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Protective Effects of BML-111 on Cerulein-Induced Acute Pancreatitis-Associated Lung Injury via Activation of Nrf2/ARE Signaling Pathway

The aim of this study was to investigate whether BML-111 can exert protective effects on cerulein-induced acute pancreatitis-associated lung injury (APALI) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway. Severe acute pancreatitis (SAP) was established by intraperitoneal injection of cerulein (50μg/kg) seven times at hourly intervals and Escherichia coli lipopolysaccharide (10mg/kg) once after the last dose of cerulein immediately. BML-111 (1mg/kg) was administered 1h before the first injection of cerulein. Samples were taken at 3, 6, 12, and 24h after the last injection. Pathologic lesions of the pancreas and lung tissues as well as the levels of serum amylase were analyzed; Myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and quinone oxidoreductase-1 (NQO1) of lung tissue were determined. The findings revealed that the injuries of pancreas and lung were typically induced by cerulein. The administration of BML-111 reduced the levels of serum amylase, lung MPO, lung MDA, the wet-to-dry weight ratio, and the pathology injury scores of the lung and pancreas, which increased in the SAP group. The expressions of Nrf2, HO-1, NQO1, and activity of SOD in lung tissue increased in the BML-111 group compared with those in the SAP group. This study indicates that BML-111 may play a critical protective role in APALI induced by cerulein. The underlying mechanisms of protective role may be attributable to its antioxidant effects through the activation of Nrf2/ARE pathway.

Agmatine attenuates silica-induced pulmonary fibrosis

There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p < 0.001) and reduced glutathione (p < 0.05) activities with significant decrease in the lung malondialdehyde (p < 0.001) content as compared to the silica group. Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects.

The acute antinociceptive effect of hyperbaric oxygen is not accompanied by an increase in markers of oxidative stress

AimsExposure to hyperbaric oxygen (HBO2) causes an antinociceptive response in mice. However, breathing oxygen (O2) at an elevated pressure can potentially cause oxygen toxicity. The aim of this study was to identify the determinants of HBO2 antinociception and the toxicity profile of HBO2. Main methodsMale NIH Swiss mice were assessed for acute antinociceptive responsiveness under room air or 100% O2 at 1.0 or 3.5 atmospheres absolute (ATA), using the acetic acid-induced abdominal constriction test. For the oxygen toxicity test, mice were exposed to 3.5 ATA oxygen for 11min, 60min, and 60min daily for 2days (120min) or 60min daily for 4days (240min), then assessed by analyzing the levels of two oxidative stress markers, MDA (malondialdehyde) and protein carbonyl in brain, spinal cord and lung. Key findingsOnly the combination of 100% O2 and 3.5 ATA caused significant antinociception. The antinociceptive effect of 100% O2 was pressure-dependent up to 3.5 ATA. In the oxygen toxicity test, mice exposed to HBO2 for different time intervals had levels of brain, spinal cord and lung MDA and protein carbonyl that were comparable to that of control animals exposed to room air. SignificanceTreatment with 100% O2 evokes a pressure-dependent antinociceptive effect. Since there was no significant increase in levels of the oxidative stress markers in the tested tissues, it is concluded that HBO2 at 3.5 ATA produces antinociception in the absence of oxidative stress in mice.

Role of Ethyl Pyruvate in Systemic Inflammatory Response and Lung Injury in an Experimental Model of Ruptured Abdominal Aortic Aneurysm

Objectıve. The purpose of this study is to evaluate the effect of ethyl pyruvate (EP) on systemic inflammatory response and lung injury in an experimental rat model of ruptured abdominal aortic anurysm (RAAA). Methods. Anaesthetized 30 Sprague-Dawley male rats were randomized to sham (Sh n : 6) (Sh + EP n : 6) or shock and clamp (S/C) groups (S/C n : 9) (S/C + EP n : 9). In the S/C and S/C + EP groups, hemorrhagic shock, lower torso ischemia, and reperfusion were created, S/C group was given 1 mL saline and S/C + EP group was given 40 mg/kg EP. At the end of reperfusion process some biochemical and histological parameters were studied in serum and lung tissues. Results. An increase was observed in all parameters except interleukin-6 (IL-6) in the S/C group in comparison to the sham groups. In the S/C + EP group, serum myeloperoxydase (MPO), malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α) as well as lung MPO and MDA values decreased significantly (P < 0.016). In the lung tissues, histological injury scores and lung tissue wet/dry ratio were significantly decreased in the S/C + EP group as compared to the S/C group (P < 0.016). Conclusions. Ethyl pyruvate may reduce systemic inflammatory response and lung injury which resulted from shock and ischemia/reperfusion in an experimental model of RAAA.

Inhalation injury and burn trauma: an experimental investigation of oxidative stress and histopathology

ABSTRACT Smoke inhalation injury is associated with high incidence of pulmonary complications as it represents a major cause of mortality after major burn injury. Burn is associated with release of inflammatory mediators which ultimately cause local and distant pathophysiological effects. The present study investigated the effect of smoke inhalation or\and burn injury on the antioxidants status in the lungs in a rat model to simulate an inhalation injury as might be encountered by firefighters and burn victims. Seventy five rats were equally randomized to five groups: Sham group, smoke inhalation injury group, burn group, sham burn group, and smoke burn group. At the end of the exposure protocol rats were killed by cervical decapitation and the lungs were removed completely and processed for histopathological and biochemical analysis by measuring lung antioxidant enzyme activities: Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPs) level, as an index of lipid peroxidation. Grossly, results showed that rats´lungs in the smoke inhalation group and the smoke burn group showed multiple hemorrhagic spots. Light microscopic examination showed localized and diffuse alveolar hemorrhage. Two rats in the burn group had evidence of pneumonia and lung abscesses. Biochemically, results showed that both smoke inhalation and burn injury significantly elevated lung MDA and glutathione peroxidase levels when compared with controls. The combined smoke and burn group resulted in a more significant rise in both antioxidant levels indicating a higher level of lipid peroxidation. SOD level was significantly lowered on exposure to both conditions when compared to control. SOD level was significantly lower in the combined injury group when compared to either smoke or burn alone. In conclusion; the above data provide evidence that inhalation injury with and without burn decrease tissue antioxidant capacity and increase tissue peroxidative injury.

Expression of the 78 kD glucose-regulated protein is induced by endoplasmic reticulum stress in the development of hepatopulmonary syndrome

ObjectiveThis study is to explore the role of 78kD glucose-regulated protein (GRP78) in the development of hepatopulmonary syndrome (HPS) in rats. MethodsThe rat model of liver cirrhosis and HPS were induced with multiple pathogenic factors. Hematoxylin and eosin (H & E) staining was performed to detect the pathological changes of the lung and liver tissues. The levels of alanine transferase (ALT), endotoxin, and tumor necrosis factor-α (TNF-α) in plasma and TNF-α and malondialdehyde (MDA) in lung tissues were detected. RT-PCR and Western blotting were conducted to detect the mRNA and protein expression levels of GRP78 in lungs. ResultsThe plasma endotoxin level was gradually increased as HPS developed, and the mRNA and protein expression levels of GRP78 in lungs were also increased as the disease progressed. The levels of ALT and TNF-α in plasma and the contents of TNF-α and MDA in lung tissues were gradually increased along with the disease progression, with a strong positive correlation. Compared with controls, the plasma TNF-α level and the mRNA and protein expression levels of GRP78 in lung tissues were significantly higher in rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in lungs were significantly higher in rats with HPS than controls. ConclusionsThe increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS, which may play an important role in the disease pathogenesis.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

Protective effects of recombinant human brain natriuretic peptide against LPS-Induced acute lung injury in dogs

Acute lung injury (ALI) is a common component of systemic inflammatory disease without more effective treatments. However, recent studies have demonstrated that the recombinant human brain natriuretic peptide (rhBNP) has anti-inflammatory effects. Therefore, we found that rhBNP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a dog model. Dogs were injected with LPS and subjected to continuous intravenous infusion (CIV) of saline solution or rhBNP. We detected the protective effects of rhBNP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) activity. Histological examination indicated marked inflammation, edema and hemorrhage in lung tissue taken 12h after rhBNP treatment compared with tissue from dogs which received saline treatment after LPS injection. LPS injection induced cytokine (IL-6 and TNF-α) secretion and lung MPO and MDA activities, which were also attenuated by rhBNP treatment. Inductions of IL-6 and TNF-α were significantly attenuated in the L-rhBNP and the H-rhBNP groups. The ratios of the L-rhBNP group and H-rhBNP group were lower than that in the lung injury group. Furthermore, MPO and MDA activities were significantly lower in the H-rhBNP group compared to those in the LI group. Our data indicate that rhBNP treatment may exert protective effects and may be associated with adjusting endogenous antioxidant enzymes. Thus, rhBNP may be considered as a therapeutic agent for various clinical conditions involving lung injury by sepsis.

The Diagnostic Value of Serum Ischemia-modified Albumin Levels in Experimentally Induced Carbon Monoxide Poisoning and Their Correlation With Poisoning Severity

The objectives were to determine the diagnostic value of blood ischemia-modified albumin (IMA) levels in experimentally induced carbon monoxide (CO) poisoning and to analyze their correlation with poisoning severity. Thirty-six female rats were randomly assigned to one of three groups: I (control group), II (low-dose CO poisoning group), and III (high-dose CO poisoning group). The control group was kept in room air, while groups II and III were exposed to 3 L/min of 3,000 ppm and 3 L/min of 5,000 ppm CO gas for 30 minutes, respectively. Serum carboxyhemoglobin (COHb), IMA, and malondialdehyde (MDA) levels; brain, heart, lung, liver, and kidney tissue MDA measurements; and histopathologic damage scores were then compared. IMA levels were significantly higher in groups II and III than in group I. A moderate positive correlation was observed between COHb and IMA levels. There was a strong positive correlation between COHb levels and degree of damage in all organs, but IMA and MDA levels did not reflect a similar correlation. Ischemia-modified albumin levels are higher in rats exposed to CO. This indicates that IMA levels can potentially be important in the diagnosis of exposure to CO or of CO poisoning. However, IMA levels are not a good biochemical marker in terms of determining the severity of poisoning.

Protective effects of methyl palmitate against silica-induced pulmonary fibrosis in rats

Silicosis is one of the most prevalent chronic occupational pulmonary diseases worldwide. The present study aimed to investigate the effects of methyl palmitate on silica-induced lung fibrosis in rats and explore the possible mechanisms. Male Sprague-Dawley rats were divided into 3 groups: group I served as control and group II served as positive control where rats were intranasally instilled with a single dose of silica suspension (50mg in 0.1ml saline/rat). Rats of group III received methyl palmitate (300mg/kg, I.P. three times per week at alternating days) for 60days after instillation of silica. At the end of the treatment period, animals were sacrificed then biochemical parameters and histopathology were assessed. Treatment with methyl palmitate attenuated silica-induced lung inflammation and fibrosis, as it significantly decreased lactate dehydrogenase (LDH) activity and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid (BALF). Methyl palmitate significantly reduced collagen deposition as indicated by a decrease in lung hydroxyproline content and marked attenuation in silica-induced lung fibrosis in histopathological results. In addition, methyl palmitate significantly increased superoxide dismutase (SOD) and reduced glutathione (GSH) activities with a significant decrease in the lung malondialdehyde (MDA) content. Methyl palmitate also reduced silica mediated overproduction of pulmonary nitrite/nitrate (NO2(-)/NO3(-)). Importantly, methyl palmitate decreased the level of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in the lung. Taken together, these results demonstrate the potent protective effects of methyl palmitate against silica-induced lung fibrosis. This effect can be attributed to methyl palmitate's ability to counteract the inflammatory cells' infiltration and hence reactive oxygen species (ROS) generation and regulate cytokine effects.

Methyl palmitate attenuates lipopolysaccharide-induced acute lung injury in mice.

The study is aimed to determine the beneficial effects of methyl palmitate (MP) which has antioxidant and anti-inflammatory effects demonstrated on murine model of acute lung injury induced by lipopolysaccharide (LPS). Forty male BALB/C mice were randomly allocated into four groups (n=10, each): control group, methyl palmitate group (300 mg/kg), LPS group, and methyl palmitate -treated groups. Methyl palmitate or vehicle was given with an intraperitoneal administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of the Adnan Menderes University. Methyl palmitate pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Methyl palmitate pretreatment also reduced the concentrations of malondialdehyde in lung tissues. This study indicates that methyl palmitate may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may involve the inhibition of NF-κB. activation.