Assessment of DNA damage and oxidative stress among traffic conductors and coal miners

Objective: To assess the DNA damage and oxidative stress among traffic conductors and coal miners. Methods: An analytical cross-sectional survey was conducted in Karak, Pakistan from March to October 2019. A total of 240 individuals participated in the study with an age range between 17 to 55 years. Among the total sample, 60 participants had exposure to traffic pollution while 60 were mine workers. Two control groups, consisting of 60 individuals each, were also recruited for comparison with the two exposure groups. Comet assay protocols were performed for assessing DNA damage and oxidative stress (length of DNA tail, levels of Superoxide Dismutase (SOD), Malondialdehyde (MDA) and Glutathione (GSH)). Data was analyzed using T-test on statistix 9.0 software. Results: The DNA tail length in traffic conductors ranged from 26.83-30.55µm (Mean=28.69 µm while their control group had DNA tail length of 7.98-9.26µm (Mean= 8.62). There was significant difference (P <0.001) between exposure and control group. The DNA length recorded in coal mine workers and their control group was ranged from 29.06-31.26µm (Mean=30.16µm) and 9.42-10.22µm (Mean=9.82), respectively. There was significant difference (P <0.001) between the two groups. As compared to control groups, both exposure groups have high levels of Superoxide Dismutase and Malondialdehyde and low levels of Glutathione. The finding was statistically significant (P <0.001). Conclusion: Increased inhalational exposure to air pollutants via working in traffic or coal mines can impose higher oxidative stress and DNA damage among workers as compared to the general population. doi: https://doi.org/10.12669/pjms.37.2.2848 How to cite this:Ullah I, Zahid M, Jawad M, Arsh A. Assessment of DNA damage and oxidative stress among traffic conductors and coal miners. Pak J Med Sci. 2021;37(2):---------. doi: https://doi.org/10.12669/pjms.37.2.2848 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Effects of manganese on fat snook Centropomus parallelus (Carangaria: Centropomidae) exposed to different temperatures

Neotropical Ichthyology ◽

10.1590/1982-0224-20170054 ◽

2017 ◽

Vol 15 (4) ◽

Cited By ~ 5

Author(s):

Bárbara Louise L. Tuzuki ◽

Frederico Augusto C. Delunardo ◽

Luciana N. Ribeiro ◽

Caroliny P. de Melo ◽

Levy Carvalho Gomes ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Control Group ◽

Glutathione S Transferase ◽

Control Groups ◽

Respective Control ◽

Significant Difference ◽

Different Temperatures ◽

Major Increase ◽

Fat Snook

ABSTRACT This study evaluates the effects of exposure to manganese (Mn2+) for 96 hours at two different temperatures (24 and 27°C) on juveniles of Centropomus parallelus through the activities of glutathione S-transferase (GST) and catalase (CAT), micronuclei test (MN) and comet assay. The GST activity did not show any significant difference between the groups exposed to Mn2+ and the respective control groups; in contrast, a major increase in the CAT activity was observed at 27°C in the group exposed to Mn2+ compared to the control group. The genotoxic analyses showed that in all animals exposed to Mn2+, the number of red cells with micronuclei increased significantly compared to the respective control groups. There was also a significant increase in the incidence of DNA damage in the groups exposed to Mn2+. At a temperature of 24ºC, animals exposed to Mn2+ had more DNA damage than those at 27°C. It is likely that the increase in temperature can also induce oxidative stress. Thus, we conclude that manganese is toxic to the fat snook juveniles, causing genotoxic damage, and when associated with an increase in temperature, manganese can also provoke an increase in oxidative stress.

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The Effect of Herniarin on Spatial Working Memory, Pain Threshold, and Oxidative Stress in Ischemic Hypoperfusion Model in Rats

Caspian Journal of Neurological Sciences ◽

10.32598/cjns.7.24.5 ◽

2021 ◽

Vol 7 (1) ◽

pp. 42-50

Author(s):

Zahra Nazari Barchestani ◽

◽

Maryam Rafieirad ◽

Keyword(s):

Oxidative Stress ◽

Pain Threshold ◽

Male Rats ◽

Control Group ◽

Tail Flick ◽

Pain Thresholds ◽

Ischemic Group ◽

Significant Difference ◽

The Brain ◽

And Oxidative Stress

Background: Ischemia causes severe neuronal damage and induces oxidative stress, memory impairment, and reduces pain threshold. Herniarin is a powerful antioxidant. Objectives: This study aimed to evaluate the effect of herniarin on memory, pain, and oxidative stress in an ischemia model in male rats. Materials & Methods: In this study, 50 male rats were divided into 5 groups of control, sham, ischemic, and two other ischemic groups, which received herniarin at doses of 150 and 300 mg/kg by gavage for 14 days. Behavioral tests were performed by shuttle box, and Y-maze and pain tests were performed by Tail-Flick test. Then, the rats’ brains were extracted to evaluate lipid peroxidation and measure the levels of thiol and Glutathione Peroxidase (GPX) in the hippocampus and striatum tissues. The results were expressed as Mean±SEM and then analyzed using suitable statistical methods of ANOVA and least significant difference post-hoc test in SPSS V. 20. Results: Herniarin significantly increased the avoidance memory, spatial memory, and pain thresholds of ischemic rats at different concentrations (P<0.001). Besides, the amount of malondialdehyde (MDA) and thiol in the ischemic group increased significantly in comparison to the control group (P<0.001). Also, in the ischemic group, GPX (P<0.001) significantly decreased. Decreased MDA (P<0.001) and thiol (P<0.001) and increased GPX levels were observed with herniarin administration (P<0.01). Conclusion: According to this study’s results, herniarin can remove free radicals and oxidant substances from the brain. Thus, it improves memory and pain thresholds in the brain hypoperfusion ischemia model.

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Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice

Biology of Reproduction ◽

10.1093/biolre/ioab114 ◽

2021 ◽

Author(s):

Paulina Nguyen-Powanda ◽

Bernard Robaire

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Dna Repair ◽

Superoxide Dismutase ◽

Germ Cells ◽

Superoxide Dismutase 1 ◽

Male Germ Cells ◽

Dna Repair Mechanisms ◽

Repair Mechanisms ◽

And Oxidative Stress

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

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Chlorella Vulgaris Biomass Supplementation Increased the Abundance of Hepatic Antioxidant Proteins in Relation to Oxidative Stress Reduction in Rabbits

10.21203/rs.3.rs-67743/v1 ◽

2020 ◽

Author(s):

Akeem Babatunde Sikiru ◽

Arangasamy Arunachalam ◽

Stephen Sunday Acheneje Egena ◽

Sejian Veerasamy ◽

Ippala Janardhan Reddy ◽

...

Keyword(s):

Oxidative Stress ◽

Chlorella Vulgaris ◽

Molecular Mechanisms ◽

Profile Analysis ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Control Groups ◽

Antioxidant Genes ◽

Significant Difference ◽

Antioxidant Proteins

Abstract Background Chlorella vulgaris is a unicellular microalga that is rich in antioxidant, its supplementation has been reported to reduce oxidative stress via upregulations of antioxidant genes. However, there are scarce reports on its effect on antioxidant protein expressions in rabbits – a situation which necessitate an untargeted proteomic profile analysis due to its supplementation. This is because untargeted proteomics profiling is an approach suitable for assessing the effectiveness of genes code translation into polypeptide chains folded into functional proteins used for specific sub-cellular or extracellular physiological activities. It remains one of the comparative avenues for evaluating the efficacies of drugs and nutraceutical agents including antioxidants. In this study, the antioxidant efficacy of a microalga Chlorella vulgaris was evaluated at molecular levels using its hepatic protein expression in rabbit models. Results After 120 days of the microalga supplementation, protein was extracted from liver of the rabbits for untargeted proteomics profiling using LC-MS/Orbitrap Fusion Tribrid™ peptides quantifier and sequencer. There were five-hundred and eleven (511) proteins identified; and among the proteins, 191 were specific to the control group while 186 were specific to the Treatment group; and 134 were common to both groups. Independent samples t-test of the protein abundance indicated that there was a significant difference (p = 0.01) between the treatment and the control groups. There was also a significant reduction in the malondialdehyde concentrations (p = 0.01), higher total antioxidant capacities (p = 0.002), and increased antioxidant enzyme activities (p = 0.05) between the treatment and control groups.Conclusion The study concluded that one of the molecular mechanisms associated with Chlorella vulgaris intake reduction of the hepatic oxidative stress is increased abundances of antioxidant proteins and reduction of the lipid peroxidation and these led to a suggestion that the microalga is a potent antioxidant agent suitable for protecting against oxidative stress in rabbits and other domestic food producing animals.

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Hyperthermia Affects Immune and Oxidative Stress Indices of Immune Organs of Broilers by Changing the Expressions of ABCG2, SVCT-2 and MCU

10.21203/rs.3.rs-936596/v1 ◽

2021 ◽

Author(s):

Xiuheng Xue ◽

Chunhuan Ren ◽

Luping Wang ◽

Mengzhu Xu Xu ◽

Caiyun Fan ◽

...

Keyword(s):

Oxidative Stress ◽

Heat Stress ◽

Immune Function ◽

Immunoglobulin M ◽

Control Group ◽

Rt Pcr ◽

Stress Group ◽

Immune Organs ◽

Significant Difference ◽

And Oxidative Stress

Abstract Background: As global temperatures rise, heat stress has become one of the major environmental stressors in the poultry industry. The purpose of the study was to investigate the effects of heat stress on immune function and oxidative stress, and further reveal the possible mechanisms of oxidative stress induced by heat stress for thymus and spleen of broilers. Methods: At the age of 28 days, thirty broilers were randomly divided into the control group (25 ± 2°C; 24 h/day) and the heat stress group (36 ± 2°C; 8 h/day); the experience was lasted for 1 week. At the end of the experience, the broilers per group were respectively euthanized and collected some samples, then to be analyzed. Results: The results showed that the levels of heat shock proteins 70 (HSP70,P＜ 0.01), corticosterone (CORT,P＜ 0.01), the contents of malondialdehyde (MDA, P＜ 0.05), interleukin-6 (IL-6, P＜ 0.01) and tumor necrosis factor-alpha (TNF-α, P＜ 0.01) in serum were significantly higher in heat stress group than that in the control group; The activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and contents of glutathione (GSH) in heat stress group significantly reduced (P＜ 0.05) in serum. Compared with the control group, the birds subjected to heat stress reduced the weight (P＜ 0.01) and the indices of thymus (P＜ 0.01), the activities of T-AOC (P＜ 0.01) and SOD (P＜ 0.05) of spleen, and levels of IL-10 (P＜ 0.05) and the GSH-PX (P＜ 0.05) in thymus and spleen, and increased the IL-6 content of thymus (P＜ 0.05), the MDA content (P＜ 0.01), and the reactive oxygen species (ROS) levels (P＜ 0.01) in thymus and spleen. Moreover, the expression of immunoglobulin G (IgG) gene in thymus and spleen of heat stressed broiler significantly increased by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR (qRT-PCR; P＜ 0.05); However, the expression of immunoglobulin M (IgM) gene in spleen significantly increased (P＜ 0.05), and had no significant difference (P＞ 0.05) in thymus of heat-stressed broiler. Furthermore, the relative expression of ATP binding cassette subfamily G member 2 (ABCG2) in thymus and spleen (P＜ 0.05), sodium dependent vitamin C transporter-2 (SVCT-2, P＜ 0.01) and mitochondria calcium uniporter (MCU, P＜ 0.01) mRNA in thymus of heat stressed broilers significantly increased; and the expression of ABCG2 (P＜ 0.05), SVCT-2 (P＜ 0.01) and MCU (P＜ 0.01) protein of thymus and spleen in the heat-stressed broiler increased significantly compared with the control group. Conclusions: In summary, the study confirmed that heat stress caused oxidative stress to immune organs of broilers, further reduced immune function. Moreover, the potential mechanisms of heat stress-induced oxidative stress for thymus and spleen was further reveal in broilers.

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Effects of Three Types of Massage on Serum Levels of Malondialdehyde, Superoxide Dismutase and Glutathione Peroxidase After One Session of Exhaustive Exercise in Female Futsal Players

Complementary Medicine Journal ◽

10.32598/cmja.10.4.631.2 ◽

2021 ◽

Vol 10 (4) ◽

pp. 328-339

Author(s):

Bahare Heydari ◽

◽

Mohsen Ghofrani ◽

Mohammad Ebrahim Bahram ◽

◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Glutathione Peroxidase ◽

Recovery Period ◽

Serum Levels ◽

The Body ◽

Exhaustive Exercise ◽

Oxidative Stress Marker ◽

Control Group ◽

Significant Difference

Objective: The production of reactive oxygen species in exercise causes oxidative stress which disturbs the balance of oxidants and antioxidants, causing destructive effects on cells. The present study aims to investigate the effect of three types of massage (Swedish, Russian, Thai) on serum levels of Malondialdehyde (MDA), Glutathione Peroxidase (GPX) and Superoxide Dismutase (SOD) following one session of exhaustive exercise. Methods: This quasi-experimental study was conducted on 48 female futsal players aged 17-22 years in Zahedan, Iran who were selected using a purposive sampling method, and randomly divided into four groups of Swedish massage (Long strokes with pressing and tapping using hands), Russian massage (Medium to high pressure), Thai massage (Pressure to certain parts of the body) and Control. The exercise program was based on Bruce protocol. Serum levels of MDA, GPX and SOD were measured by before and immediately after exercise and after massage. Data analysis was performed using repeated measures ANOVA, considering a significance level of P≤0.05. Results: In all three types of massage, there was a significant decrease in serum level of MDA (0.22±0.08), and a significant increase in GPX (1.84±0.46) and SOD (10.02±2.86) levels after exhaustive (P=0.001). No significant difference was observed in the control group. Conclusion: It seems that Russian, Thai, and Swedish types of massage can affect the serum levels of the MDA (as an oxidative stress marker) and the antioxidant enzymes of GPX and SOD during the post-exercise recovery period.

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The Effects of Melatonin and Propolis on Markers of Inflammation, Oxidative Stress, Clinical Outcomes, and Survival Rate in Patients with Primary Sepsis Hospitalized in Intensive Care Unit: A Randomized Clinical Trial

10.21203/rs.3.rs-56718/v1 ◽

2020 ◽

Author(s):

Naseh Pahlavani ◽

Alireza Sedaghat ◽

Gordon A Ferns ◽

Mahdie Mir ◽

Mahsa Malekahmadi ◽

...

Keyword(s):

Oxidative Stress ◽

Clinical Trial ◽

Survival Rate ◽

Clinical Outcomes ◽

The Body ◽

Calorie Intake ◽

Control Group ◽

Control Groups ◽

Markers Of Inflammation ◽

And Oxidative Stress

Abstract Background: Systemic Inflammatory Response Syndrome (SIRS) that occurs under stressful conditions affecting all organs of the body. Previous studies have shown that propolis and melatonin have the potential to improve inflammation and oxidative stress, so the aim of this study was to investigate the effects of these supplements on SIRS treatment.Method: This was a randomized, controlled clinical trial in SIRS patients comprising 55 subjects that were randomly assigned to 3 intervention or control groups. In the 3 intervention groups, patients were treated with propolis alone (at dose of 1000 mg/day), propolis (1000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day) respectively, while there was no intervention in the control group. The inflammatory and oxidative stress markers and clinical outcomes were measured before and after of the intervention, also 28-day survival rate was assessed. Results: Propolis plus melatonin reduced serum interleukin 6 (p = 0.001) and CRP levels (p <0.001), and was associated with an increased gavage intake (p = 0.016). At the end of the study, there was no difference between the groups in the oxidative stress and hematological indices. In the propolis+melatonin group, the clinical outcomes were significantly improved (p <0.05). Also the SOFA score between the groups did not differ at any time, its changes was significant during the time (p>0.001). The average survival after 28 days of follow-up in the propolis, propolis+melatonin, melatonin and control groups were 24.08, 25.69, 22.05 and 19.42 days respectively, although this was not statistically significant (p=0.07).Conclusion and relevance: Supplementation with propolis+melatonin may help to improve clinical outcomes by reducing inflammation and was probably associated with an increase in the calorie intake, leading to an increase in the survival rate in SIRS patients, although more studies are necessary to prove these effects. Trial registration: IRCT20181025041460N1.

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Evaluation of oxidant and antioxidant status in infants with hyperbilirubinemia and kernicterus

Human & Experimental Toxicology ◽

10.1177/0960327111401638 ◽

2011 ◽

Vol 30 (11) ◽

pp. 1751-1760 ◽

Cited By ~ 10

Author(s):

Murat Doğan ◽

Erdal Peker ◽

Ercan Kirimi ◽

Ertan Sal ◽

Sinan Akbayram ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Status ◽

Sulfhydryl Group ◽

Stress Index ◽

Control Group ◽

Significant Difference ◽

Group 2 ◽

And Control ◽

And Oxidative Stress ◽

Group 1

Objective: The objective of the present study was to determine oxidant and antioxidant status in infants with hyperbilirubinemia and/or kernicterus and to find whether there is a relationship between bilirubin level and oxidant/antioxidant status. Patients: The study includes 69 full-term newborns (neonates with hyperbilirubinemia needing phototherapy [Group 1, n = 36] and neonates with kernicterus [Group 2, n = 33]) and 25 age-matched healthy newborn. Results: Plasma total antioxidant capacity (TAC) and serum total oxidant status (TOS) were significantly higher in Groups 1 and 2 than the control group. There was a significant difference between Group 1 and control cases for malondialdehyde (MDA; p < 0.001). Total free sulfhydryl group (TTHI) values were significantly elevated in Group 1 compared to Group 2 and control cases. Correlation analysis showed that the correlation between total bilirubin (TB) and TAC, TOS, MDA and oxidative stress index may be expressed by a quadratic curve. After phototherapy, a statistically significant increase in nitrite level was observed. Conclusion: We demonstrated that the relationship between serum TB and antioxidants and oxidative stress could be expressed by a quadratic correlation curve.

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Investigating the Effect of Fresh Frozen Plasma and Albumin on DNA Damage and Oxidative Stress Biomarkers in Poisoning Cases by Organophosphates

Drug Research ◽

10.1055/a-1261-9151 ◽

2020 ◽

Vol 71 (01) ◽

pp. 10-16

Author(s):

Saeed Afzali ◽

Manoochehr Karami ◽

Nejat Kheyripour ◽

Akram Ranjbar

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Fresh Frozen Plasma ◽

Adjunctive Treatment ◽

Control Group ◽

Oxidative Stress Biomarkers ◽

Significant Difference ◽

Antioxidant Parameters ◽

Fresh Frozen ◽

Frozen Plasma

AbstractThe efficacy of albumin and fresh frozen plasma (FFP) and their effects on biomarkers of oxidative stress has been evaluated. In a randomized clinical control trial, 33 poisoned patients by Organophosphate (OP) were enrolled in the research and divided into three groups. The first group underwent conventional treatments by atropine and pralidoxime (control group); the second and third groups, in addition to traditional treatments, received albumin and FFP. Cholinesterase (ChE) enzyme activity, total antioxidant capacity (TAC), serum thiol groups (TTG), malonyl aldehyde (MDA) and DNA damage were measured in all treatment and control groups. Patients were matched in terms of demographic characteristics at the beginning of the study. ChE activity was increased in all three groups during treatment, which was more noticeable in the FFP group and was statistically significant in both albumin and FFP group compared to the control group (p<0.05). TAC increased, and TTG decreased in FFP and albumin groups compared to the control group; no significant difference was observed. MDA decreased in albumin and FFP and was significantly different in the FFP group compared to the control group (p<0.05). The amount of DNA damage in FFP and albumin groups decreased, and there was a significant difference compared to the control group (p<0.05). According to the results of this study, due to the decrease of oxidative damage parameters and the increase of antioxidant parameters in albumin and specially FFP groups, FFP may be considered as an adjunctive treatment for OP poisoning.

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Rosuvastatin Affects Tracheal Responsiveness, Bronchoalveolar Lavage Inflammatory Cells, and Oxidative Stress Markers in Hyperlipidemic and Asthmatic Rats

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i6.2175 ◽

2020 ◽

Author(s):

Saeideh Saadat ◽

Amin Mokhtari-Zaer ◽

Mousa-Al-Reza Hadjzadeh ◽

Mohammad Hossein Boskabady

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Bronchoalveolar Lavage ◽

Control Group ◽

Oxidative Stress Markers ◽

Total Thiol ◽

Stress Markers ◽

Thiol Content ◽

Wbc Count ◽

And Oxidative Stress

Statins provide greater protection than predicted from just cholesterol-lowering effects, which is possibly mediated by other pleiotropic actions. This study aimed to examine the possible interaction effect of asthma on lipid profiles and evaluate the effect of rosuvastatin treatment on asthma. The animals were assigned into (1) control, (2) asthmatic, (3) hyperlipidemic, (4) asthmatic-hyperlipidemic, (5) rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic, (6) rosuvastatin-treated hyperlipidemic and (7) rosuvastatin-treated asthmatic-hyperlipidemic groups. Tracheal responsiveness to methacholine and ovalbumin, total and differential WBC (white blood cell) counts, and oxidative stress markers in bronchoalveolar lavage fluid (BALF) were evaluated. In the asthmatic and asthmatic-hyperlipidemic groups, tracheal responsiveness to ovalbumin, total WBC count, numbers of eosinophils, neutrophils, and monocytes were higher than the control group (p<0.001). A left-ward shift in the concentration-response curves to methacholine, an increase in nitrite and malondialdehyde concentrations, and a decrease in total thiol content, superoxide dismutase and catalase activities were also observed in the asthmatic and asthmatic-hyperlipidemic groups compared to control group (p<0.01 to p<0.001). Beyond lipid-lowering effect in the treated hyperlipidemic and asthmatic-hyperlipidemic groups, rosuvastatin treatment decreased tracheal responsiveness to methacholine, reduced total WBC count, the numbers of eosinophils, neutrophils, and monocytes, as well as decreased malondialdehyde concentration, and increased total thiol content, superoxide dismutase and catalase activities in treated asthmatic and asthmatic-hyperlipidemic groups (p<0.05 to p<0.001). The improving effect of rosuvastatin on asthmatic and asthmatic-hyperlipidemic animals was shown due to pleiotropic mechanisms including the effect on airway hyperresponsiveness, lung inflammation, and oxidative stress.

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