Lung Malondialdehyde Levels Research Articles

Ficus carica Puree Exerts a Higher Antioxidative Profile in Hypoxic Lungs after Intermittently Inducing Hypoxia in Sprague–Dawley Rats

Abstract Background: The body produces more hypoxia-inducible factor and reactive oxygen species in response to hypoxic situations because they cause unbalanced oxygen levels. Ficus carica provides numerous benefits because of its high antioxidant and mineral content. Nevertheless, the mechanism by which F. carica consumption confers this protective benefit remains incompletely understood. Aim: This study aimed to evaluate how F. carica puree (FCP) can affect the antioxidant enzyme activity and malondialdehyde (MDA) levels in the lung by mitigating the effects of intermittent hypoxia (IH). Methods: Thirty Sprague–Dawley rats were divided into five groups negative control (NC), untreated; positive control (PC), treated with aquadest; FCP1; FCP2; and FCP3, which received FCP at doses of 1.25, 2.5, and 5 mL/200 g body weight. The treatment was administered for 4 weeks before inducing IH (10% O2 and 90% N2) into all groups (except NC) for 4 h for 7 days. Furthermore, hemoglobin (Hb) level, lung MDA level, and lung superoxide dismutase (SOD) enzyme activity were assessed. Results: The Hb level did not exhibit a significant increase under IH conditions. Conversely, the PC group exhibited the least activity of lung antioxidant enzymes and the highest lung MDA levels. In addition, the FCP intervention group exhibited lower MDA levels than the PC group and ameliorated relative lung weight loss. Conclusion: All FCP intervention groups showed lower MDA levels and higher SOD levels compared to the PC group, suggesting that FCP could mitigate the effects of hypoxia in rat lungs.

Etanercept’s Protective Effect Against Lung Inflammation Caused by Polymicrobial Sepsis Induced by CLP in Male Rats

Inflammation and oxidative stress are critical factors leading to sepsis-induced severe lung injury (ALI). This study investigates the regulatory effects of Etanercept (ENT) in an animal model of sepsis-induced ALI. We established a cecal ligation and puncture (CLP) model for ALI in adult rats under anesthesia. Sepsis amplifies pathological lung tissue damage, lung endothelial permeability, serum inflammatory factor production, and the number of inflammatory cells in bronchoalveolar lavage fluid. Furthermore, it enhances the expression of phosphorylated NF-\(\kappa\)B p65, reduces lung superoxide dismutase due to CLP, and elevates lung malondialdehyde levels due to LPS-induced inflammatory factor production. This cascade of events exacerbates the expression of several genes, including TNF-\(\alpha\) and cytokines. LPS-induced inflammatory factor production also enhances the formation of reactive oxygen species in mitochondria. In summary, our current research provides evidence that ENT acts as a novel regulator of inflammation in sepsis-induced ALI in rats. The control of oxidative stress and the modulation of the inflammatory response are two key underlying mechanisms for the effects of ENT.

The effect of Edaravone on lung injury after lower limb ischemiareperfusion in a rat model: Biochemical and histopathological insights

Aim: Lower limb ischemia/reperfusion leads to distant organ dysfunction, notably affecting the lungs, resulting in respiratory failure and significant morbidity and mortality. Edaravone is a new free radical scavenger and has attracted the attention of researchers. This study aims to examine edaravone's influence on lung injury arising from lower limb ischemia-reperfusion. Material and Methods: Forty male Wistar rats were categorized into groups: Sham, Ischemia/Reperfusion (IR), Solvent, and Edaravone. The infrarenal abdominal aorta was clamped for 120 minutes and then reperfused for another 120 minutes. Edaravone was administered 30 minutes before the ischemic event. Then we analyzed serum and lung tissue samples for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and nitric oxide (NO) levels. Furthermore, a thorough histopathological assessment was conducted. Results: In the IR group, edaravone notably reduced serum and lung MDA levels. While significant differences in serum SOD and NO levels existed between the IR and edaravone groups, similar differences were not found in the lung tissue samples. There appeared to be no significant impact of edaravone on serum and lung GPx levels. The histopathological investigation revealed that the lung injury score was significantly higher in the IR group compared to the control group, a difference mitigated by edaravone treatment. Conclusion: Our findings suggest that edaravone mitigates lower limb ischemia-reperfusion-induced lung injury, both biochemically and histopathologically. Our findings imply the potential utility of this agent in the context of acute ischemia-reperfusion injury following vascular surgery.

Repurposing of carvedilol to alleviate bleomycin-induced lung fibrosis in rats: Repressing of TGF-β1/α-SMA/Smad2/3 and STAT3 gene expressions

Idiopathic pulmonary fibrosis (IPF) is the most widely studied interstitial lung disease. IPF eventually leads to respiratory insufficiency, lung cancer, and death. Carvedilol (CAR) is a third-generation β-adrenergic receptor antagonist with an α1-blocking effect. CAR demonstrates antifibrotic activities in various experimental models of organ fibrosis. Aims: This work is designed to explore the possible alleviating effects of CAR on bleomycin (BLM)-induced lung fibrosis in rats. Main methods: The BLM rat model of lung fibrosis was achieved by intratracheal delivery of a single dose of 5 mg/kg of BLM. Seven days following BLM injection, either prednisolone or CAR was orally administered at doses of 10 mg/kg once daily for 21 days to the rats. The actions of CAR were evaluated by lung oxidant/antioxidant parameters, protein concentration and total leucocyte count (TLC) in bronchoalveolar lavage fluid (BALF), fibrosis regulator-related genes along with the coexistent lung histological changes. Key findings: CAR effectively decreased lung malondialdehyde level, increased superoxide dismutase activity, declined both protein concentration and TLC in BALF, downregulated TGF-β1/α-SMA/Smad2/3 and STAT3 gene expressions, and repaired the damaged lung tissues. Significance: CAR conferred therapeutic potential against BLM-induced lung fibrosis in rats, at least in part, to its antioxidant, anti-inflammatory, and antifibrotic activities. CAR could be utilized as a prospective therapeutic option in patients with lung fibrosis in clinical practice.

The Beneficial Effect of the Blockade of Stim-Activated TRPC-ORAI Channels on Vascular Remodeling and Pulmonary Hypertension Induced byIntermittent Hypoxia Is Independent of Oxidative Stress.

Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associated with pulmonary hypertension (PH). Rats exposed to CIH develop systemic and lung oxidative stress, pulmonary vascular remodeling, and PH and overexpress Stim-activated TRPC-ORAI channels (STOC) in the lung. Previously, we demonstrated that 2-aminoethyl-diphenylborinate (2-APB)-treatment, a STOC-blocker, prevents PH and the overexpression of STOC induced by CIH. However, 2-APB did not prevent systemic and pulmonary oxidative stress. Accordingly, we hypothesize that the contribution of STOC in the development of PH induced by CIH is independent of oxidative stress. We measured the correlation between right ventricular systolic pressure (RVSP) and lung malondialdehyde (MDA) with the gene expression of STOC and morphological parameters in the lung from control, CIH-treated, and 2-APB-treated rats. We found correlations between RVSP and increased medial layer and STOC pulmonary levels. 2-APB-treated rats showed a correlation between RVSP and the medial layer thickness, α-actin-ir, and STOC, whereas RVSP did not correlate with MDA levels in CIH and 2-APB-treated rats. CIH rats showed correlations between lung MDA levels and the gene expression of TRPC1 and TRPC4. These results suggest that STOC channels play a key role in developing CIH-induced PH that is independent from lung oxidative stress.

Deneysel Epileptik Nöbet Modelinde, Artemisinin'in Fare Kalp ve Akciğer Dokularında Oksidatif Stress Belirteçleri Üzerine Etkisi.

Aim: The current study investigated the effects of artemisinin on the heart and lung tissue against pentylenetetrazol-induced seizures in mice. For this purpose, malondialdehyde (MDA), advanced oxidation protein products (AOPP), Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels were evaluated in both tissue homogenates.Material and Method: Swiss albino male mice (n=42) were used in the experiment. Animals were divided into six groups; Control (C), pentylenetetrazol (PTZ), valproate 100 mg/kg (VPA), artemisinin 30 mg/kg (ARS)+PTZ, ARS 60 mg/kg+PTZ, ARS 120 mg/kg+PTZ. On the 26th day of the experiment, the mice were sacrificed and the samples were kept at -80 0C for biochemical analysis.Results: There were significant differences in the five biochemical parameters analyzed in heart and lung tissues. Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups (p<0.05). Heart and lung MDA levels of the PTZ group were found to be significantly higher than the C and ARS-60 groups. Likewise, heart AOPP levels decreased significantly in the VPA and ARS-60 groups compared to the PTZ group (p<0.05). There was no significant difference between the groups in terms of lung AOPP levels (p>0.05). Heart CAT and GSH levels were decreased in the PTZ group compared to the other groups. However, in terms of Lung CAT levels, the PTZ group had the highest value compared to the other groups, while it had the lowest value in terms of GSH level. The GSH-Px level did not differ significantly between the groups in heart tissue (p>0.05). The lung GSH-Px level was significantly increased in the ARS-30 group when compared to the PTZ group (p<0.05).Conclusion: Consequently ARS treatment can inhibit PTZ-induced oxidative stress in peripheral tissues. In addition, ARS may provide improvements in decreased antioxidant enzymes. ARS may contribute to the antioxidant defense system.

Acute lung inflammation induced by zinc oxide nanoparticles: Evolution and intervention via NRF2 activator

Zinc oxide nanoparticles (ZnONPs) are widely used worldwide. Human inhalation exposure to ZnONPs induces acute lung inflammation (ALI); however, the characteristics and therapeutic targets of ALI are unclear. In this study, female C57BL/6J mice were subjected to a single intratracheal instillation of 20 μg of ZnONPs. Increased lung malondialdehyde levels and decreased total antioxidant capacity at 6 h, as well as increased lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) at 1 day (d) post treatment were observed. A significant inflammatory response was observed at 3 d and 7 d, as evidenced by increased leukocyte numbers and total protein concentration in BALF, and histological abnormalities. Pulmonary NRF2 signaling was significantly activated at 3 d post treatment. To investigate a protective role of NRF2 activator against ZnONP-induced ALI, the mice were intraperitoneally injected with 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) (2 mg/kg) 1 d before and 1 d after ZnONPs treatment. CDDO-Im significantly decreased leukocyte numbers and total protein concentration in BALF and pulmonary inflammatory gene expression, and ameliorated histopathological abnormalities induced by ZnONPs. Collectively, the present study indicates that ZnONPs exposure leads to oxidative stress, cell injury and inflammation in the lung successively. Moreover, the NRF2 activator protects against ZnONPs-induced ALI.

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury.

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90°C water bath for 10s. 100mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.

PENGARUH PEMBERIAN EKSTRAK KULIT PISANG KEPOK (Musa acuminata) TERHADAP PENURUNAN KADAR MALONDIALDEHID (MDA) PARU MENCIT JANTAN (Mus musculus) YANG DIPAPAR ASAP ROKOK

This research aimed to determine the effect of kepok banana peel extract (Musa acuminata) given by per oral in decreasing levels of malondialdehyde (MDA) in lung of male mice (Mus musculus) which was exposed to cigarette smoke. The 24 experimental male mice were divided into 6 groups. The therapy was given for 14 days, all mice were sacrificed and lung MDA level were examined with thiobarbituricacid (TBA) methods. The result of the data analysis test using one-way ANOVA (Analysis of Variance) showed that there were significant differences between the group of animals that exposed to cigarette smoke ( = 840.50± 186.47 nmol / g) and the group of animals that were given with extract of kepok banana peel 56 mg / kg bw ( = 6471.25 ± 69.25 nmol/g). Besides that, there was an significant difference between the groups of animals that were exposed cigarette smoke ( = 840.50± 186.47 nmol / g) with the group of animals that were given with vitamin C 260 mg/kg bw ( = 555.25± 61.16 nmol / g). It could be concluded that extract of kepok banana peel and vitamin C could decrease MDA levels in lung of male mice which was exposed cigarette smoke. The increased therapy dose gave affect in lowering levels of malondialdehyde in lung.

Inhibition of ERRα Aggravates Sepsis-Induced Acute Lung Injury in Rats via Provoking Inflammation and Oxidative Stress.

Inflammation and oxidative stress are critical pathologies that contribute to sepsis-induced acute lung injury (ALI). This study investigated the regulatory role of estrogen-related receptor alpha (ERRα) in an experimental model of sepsis-induced ALI. In vivo, a cecal ligation and puncture- (CLP-) induced ALI model was established in anesthetized rats. Animals were then randomly assigned to receive an intraperitoneal injection of vehicle or ERRα inverse agonist (XCT-790, 2.5 mg/kg). Administration of XCT-790 significantly aggravated a sepsis-induced increase in pathological damage of lung tissues, lung endothelial permeability, myeloperoxidase (MPO) activity in lung tissues, production of serum inflammatory factors, and inflammatory cell accumulation in bronchoalveolar lavage fluid. In addition, XCT-790 treatment exacerbated a CLP-induced decrease in lung superoxide dismutase and an increase in lung malondialdehyde levels. In vitro, the exposure of rat pulmonary microvascular endothelial cells (PMVECs) to lipopolysaccharide (LPS) resulted in increased endothelial permeability and reduced expression of tight junction protein ZO-1, Occludin, JAM-A, and adherens junction protein VE-cadherin, which were further deteriorated by knockdown of ERRα. In addition, LPS-triggered inflammatory factor production and increase in the expression of phosphorylated IκBα and NF-κB p65 were also exacerbated by silencing ERRα gene. Meanwhile, knockdown of ERRα dramatically promoted LPS-activated mitochondrial reactive oxygen species production and LPS-induced downregulation of Sirt3 protein levels in rat PMVECs. Taken together, our present study provides evidences that ERRα functions as a novel negative modulator of sepsis-induced ALI in rats. The underlying mechanisms responsible for ERRα-elicited effects are largely dependent on the regulation of inflammatory response and oxidative stress.

Vagotomy Improves Hypoxic Pulmonary Vasoconstriction in Rats Subjected to Brain Ischemia-Reperfusion Injury.

Background: Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats.Methods: This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey’s post hoc test and t test, was used to compare the variables in the experimental groups.Results: The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO2 and pH were lower, and PCO2 was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019).Conclusion: Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing.

Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis.

IntroductionEthyl pyruvate (EP), a natural flavoring and fragrance agent, has been shown to exert anti-inflammatory and antioxidant actions. We tested the potential beneficial effects of EP in a rat model of acute necrotizing pancreatitis (ANP), a serious condition with a significant inflammatory explosion and oxidative stress.Material and methodsFifty-two adult male Sprague-Dawley rats were divided into four groups: sham + saline, sham + EP, ANP + saline, and ANP + EP. The ANP was induced by glycodeoxycholic acid and cerulein. Animals were sacrificed at 48 h and biochemical, hematological, and histological markers of ANP and inflammation were assessed. The extent of mortality, systemic cardiorespiratory variables, pancreatic microcirculation, renal/hepatic functions, acinar cell injury and enzyme markers for pancreas and lung tissues were investigated.ResultsThe EP-treated ANP group presented significantly lower mortality than the untreated ANP group (44% (7/16) vs. 19% (3/16), respectively, p < 0.05). Administration of EP resulted in significantly lower levels of IL-6 (ANP + saline: 5470 ±280 vs. ANP + EP: 2250 ±180 pg/ml, p < 0.05). Compared with the ANP group, the ANP + EP group had a lower pancreatic necrosis score (1.45 ±0.2 vs. 0.96 ±0.2, p < 0.05). Moreover, intraperitoneal EP administration had a positive effect on most indices of pancreatitis (amylase and alanine transaminase levels) and lung damage (except lung malondialdehyde levels) as they decreased towards baseline values.ConclusionsThe results from this experimental study indicate that EP, a nontoxic chemical approved by the Food and Drug Administration as a food additive, provides positive effects on the course of pancreatitis, suggesting potential usefulness in management of ANP.

Protective effects of continuous positive airway pressure on a nonventilated lung during one-lung ventilation: A prospective laboratory study in rats.

The use of one-lung ventilation (OLV) to facilitate intrathoracic surgery is a cause of lung injury. We hypothesised that application of continuous positive airway pressure (CPAP) to a nonventilated lung during OLV would prevent alveolar hypoxia and blood flow shift from the nonventilated to the ventilated lung, thereby attenuating lung injury. Controlled animal study. University laboratory. Adult male Sprague-Dawley rats (n = 4 to 8 per group, depending on experiments). Rats were alternately assigned to one of two ventilation protocol groups: control and CPAP groups. Rats received 240 min of OLV followed by 240 min of two-lung reventilation (re-TLV). The nonventilated lungs of rats in the control group were collapsed during OLV whereas rats in the CPAP group received CPAP (5 cmH2O with 100% oxygen) to the nonventilated lungs. Pulmonary blood flow during OLV was measured by quantification of lung radioactivity after intravenous infusion of indium-labelled macroaggregated albumin. Inflammatory cytokines in the lungs after 240 min of OLV, and after the subsequent 240 min of re-TLV were measured. Additionally, we measured lung wet-to-dry weight ratios after re-TLV. We also measured lung malondialdehyde levels after re-TLV as an indicator of reactive oxygen species produced by reoxygenation. Application of CPAP attenuated the pulmonary blood flow shift from the nonventilated to the ventilated lung. CPAP decreased the levels of IL-6, CXC chemokine ligand-1 and CC chemokine ligand-2 in both lungs after 240 min of OLV. CPAP also decreased CXC chemokine ligand-1 in the nonventilated lung and CC chemokine ligand-2 in both lungs after re-TLV. Moreover, wet-to-dry weight ratios of both lungs were decreased by application of CPAP. However, lung malondialdehyde concentrations were not affected by CPAP. CPAP applied to the nonventilated lung during OLV suppresses blood flow shift and decreases inflammatory cytokines and water content in both lungs. Application of CPAP may attenuate lung injury during and after OLV.

Survival advantage depends on cecal volume rather than cecal length in a mouse model of cecal ligation and puncture

BackgroundCecal ligation and puncture (CLP) is the most commonly used model to simulate human polymicrobial sepsis. However, the severity of CLP is difficult to be standardized across different laboratories. The aim of the present study was to evaluate the influence of ligated cecal volume and length on mortality in mouse CLP model. MethodsCecal length and volume were measured from 120 Kunming mice subjected to CLP or sham operation. According to cecal volume, mice were divided into three groups, volume0.0∼0.2 (0.0 cm3-0.2 cm3), volume0.2∼0.4 (0.2 cm3-0.4 cm3), and volume>0.4 (larger than 0.4 cm3). The contents of cytokines, including interleukin-1β, interleukin-6, and TNF-α, were measured at 3 h after surgery. The blood bacterial load and oxidative stress indicators (including malondialdehyde and superoxide dismutase) were measured at 12 h after surgery. ResultsThere was no significant difference on 72-h survival rate between the mice with cecum longer than 2 cm and shorter than 2 cm. Compared to the other volume groups, volume>0.4 group showed significantly increased blood bacterial load, malondialdehyde levels in lung and liver, and pro-inflammatory cytokines in serum. Surprisingly, the survival rate in volume>0.4 (0%) group showed significant difference from those of volume0.0∼0.2 group (40%) and volume0.2∼0.4 group (40%). ConclusionsThe mice in volume>0.4 group have much serious inflammatory reaction and are easier to die. As the proportion of volume>0.4 mice is near 20%, it can have large influence on most of the related studies using this CLP model.

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.

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.

Colchicine Protects against Hyperoxic Lung Injury in Neonatal Rats

Background: Bronchopulmonary dysplasia (BPD) is characterized by inflammation, fibrosis and mucosal necrosis, which leads to emphysematous coalescence of alveoli. Objective: We tested whether prophylaxis with colchicine , an anti-inflammatory, antioxidant and antifibrotic drug, would decrease the severity of lung injury in an animal model of BPD. Methods: Twenty-five rat pups were divided into three groups: control (n = 8), hyperoxia (n = 7), and hyperoxia + colchicine (n = 10). The hyperoxia groups were exposed to >95% oxygen from day 1 to 10 of life. On day 10, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Lung morphology was assessed by the mean linear intercept (MLI), a measure of alveolar size. The degree of lung inflammation and antioxidant capacity were assessed by quantifying lung homogenate tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Results: Colchicine significantly decreased lung damage as determined by the MLI in the hyperoxia groups (p < 0.01). The median level of lung MDA was significantly higher in the hyperoxia group compared with the control group (p < 0.05) and the colchicine-treated group (p < 0.05). Lung homogenate SOD and GSH-Px activities in the colchicine-treated group were significantly higher than in the hyperoxia group (p < 0.05). Furthermore, colchicine-treated pups had lower lung homogenate TNF-α and IL-1β levels compared with the hyperoxia group (p < 0.05). Conclusions: Colchicine has favorable effects on alveolarization as well as inflammation and oxidative stress markers in an animal model of BPD.