Adenovirus-mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury

2004 ◽  
Vol 286 (6) ◽  
pp. L1188-L1193 ◽  
Author(s):  
Yan Wang ◽  
Yefim Manevich ◽  
Sheldon I. Feinstein ◽  
Aron B. Fisher

1-Cys peroxiredoxin (1-cysPrx) is a novel antioxidant enzyme that has been shown to reduce a broad spectrum of peroxides including phospholipid hydroperoxides. We tested the hypothesis that adenovirus-mediated transfer of the 1-cysPrx gene can protect lungs of mice from oxidant injury. Mice infected with AdLacZ/AdNull were used as a control (AdCon). X-galactosidase staining revealed widespread expression of the LacZ gene in airways and lung alveoli. Compared with AdCon, 1-cysPrx expression was increased about twofold at 3 days after adenovirus infection. Mice with increased Prx expression showed less loss of body weight and longer survival during exposure to 100% O2 or to 85% O2 for 4 days followed by 100% O2. At 72 h of 100% O2 exposure, AdPrx infection protected mouse lungs from injury as indicated by less pleural effusion, lower lung wet/dry weight, less protein and fewer nucleated cells in bronchoalveolar lavage fluid, and lower content of thiobarbituric acid-reactive substances and protein carbonyls in lung homogenate. These findings show that increased expression of 1-cysPrx through adenovirus-mediated gene transfer protects mouse lungs from hyperoxic injury and delays death.

2021 ◽  
pp. jim-2020-001768
Author(s):  
Vegi Naidu ◽  
Amir A Zeki ◽  
Pawan Sharma

The COVID-19 pandemic has affected over 114 million people and has resulted in >2.5 million deaths so far. Some people have greater susceptibility which influences both SARS-CoV-2 infectivity and COVID-19 severity. Smoking is associated with increased ACE-2, the receptor for SARS-CoV-2, which facilitates its entry through the lung. However, despite the widespread use of e-cigarettes, also known as ‘vaping’, little is known regarding the effects of vaping on ACE-2 expression and how this affects SARS-CoV-2 infection. In addition, the added effect of nicotine in the vapor is also unknown. Thus, we tested whether vaping induces ACE-2 expression in the mouse lung. BALB/c mice exposed to e-cigarette vapor (±nicotine) resulted in a significant increase in peribronchiolar inflammation and influx of immune cells into the airways. Vapor increased monocyte chemoattractant protein-1, interleukin 1β, and KC levels in bronchoalveolar lavage fluid in both sexes, which were further enhanced by nicotine (whereas increase in interleukin 6 was sex and nicotine independent). The reduction in basal inspiratory capacity with vapor exposure occurred independent of sex or nicotine. The increase in methacholine-induced airway hyper-responsiveness was independent of sex; however, in female mice it was only significant in the nicotine-exposed group. Lung ACE-2 expression was increased in male mice in a nicotine-dependent manner as compared with female mice. Collectively, while vaping (±nicotine) induced airway inflammation and impaired lung function, the induction of lung ACE-2 occurred to a significantly greater degree in males exposed to vapor containing nicotine as compared with females. Thus, via these effects on ACE-2 expression in the lungs and airways, vaping itself may facilitate SARS-CoV-2 entry into the airways.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Christonikos Leventelis ◽  
Nikolaos Goutzourelas ◽  
Aikaterini Kortsinidou ◽  
Ypatios Spanidis ◽  
Georgia Toulia ◽  
...  

Buprenorphine and methadone are two substances widely used in the substitution treatment of patients who are addicted to opioids. Although it is known that they partly act efficiently towards this direction, there is no evidence regarding their effects on the redox status of patients, a mechanism that could potentially improve their action. Therefore, the aim of the present investigation was to examine the impact of buprenorphine and methadone, which are administered as substitutes to heroin-dependent patients on specific redox biomarkers in the blood. From the results obtained, both the buprenorphine (n=21) and the methadone (n=21) groups exhibited oxidative stress and compromised antioxidant defence. This was evident by the decreased glutathione (GSH) concentration and catalase activity in erythrocytes and the increased concentrations of thiobarbituric acid reactive substances (TBARS) and protein carbonyls in the plasma, while there was no significant alteration of plasma total antioxidant capacity (TAC) compared to the healthy individuals (n=29). Furthermore, methadone revealed more severe oxidant action compared to buprenorphine. Based on relevant studies, the tested substitutes mitigate the detrimental effects of heroin on patient redox status; still it appears that they need to be boosted. Therefore, concomitant antioxidant administration could potentially enhance their beneficial action, and most probably, buprenorphine that did not induce oxidative stress in such a severe mode as methadone, on the regulation of blood redox status.


2017 ◽  
Vol 9 (9) ◽  
pp. 68
Author(s):  
Natacha Cossettin Mori ◽  
Roberta Cattaneo Horn ◽  
Caroline Oliveira ◽  
Gabriela Tassotti Gelatti ◽  
Jonathas Zeni Klafke ◽  
...  

Agrochemicals were more prominent in 1960, marked due to the agricultural modernization process. As a result of this widespread use for food production, there was also an increase in cases of intoxication caused by these agents which made it necessary to search for alternative therapies for agricultural workers. Thus, considering that phytochemical characterization revealed the presence of antioxidants in Cymbopogon citratus extract, the objective of this study was to evaluate the effect of this plant infusion on the enzyme acetylcholinesterase activity (AChE) and on the redox response in farmers’ erythrocytes. These erytrocytes were processed and subjected to treatment with the Cymbopogon citratus infusion (5, 10, 25 and 50 g/L). In these samples the following were determined: the AChE enzyme activity, the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (CPs) and reduced glutathione (GSH). In general, it was discovered that the inhibition of AChE activity is negative regarding to the increase of protein carbonyl levels and positive regarding the GSH levels. In addition, Cymbopogon citratus infusions could not even reverse this inhibition or the high levels of TBARS and CPs. On the other hand, levels of GSH were increased by infusions demonstrating the increased antioxidant activity in rural workers’ erythrocytes.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Neelam Chandra ◽  
Nalini Pandey

Black gram (Vigna mungo L. var. DPU-88-31), an edible legume, was grown at 1, 2, 4, 6, and 8 meq S L−1 to study the effect of deficient and excess level of sulfur on oxidative metabolism. Plants supplied by 4 meq S L−1 showed optimum yield. Sulfur deficient plants (1 and 2 meq S L−1) showed reduction in growth and chlorosis of young leaves. Tissue sulfur and cysteine concentration was increased with increasing sulfur supply. The thresholds for critical concentration of sulfur deficiency and toxicity were 0.315% and 0.434% dry weight. Biomass and photoassimilatory pigments were decreased and carbohydrates (sugar and starch) were accumulated in leaves of sulfur deficient and excess plants. Accumulation of hydrogen peroxide and thiobarbituric acid reactive substances in sulfur deficient and excess plants caused oxidative damage in plants which was also evident by the increase in the activity of superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, glutathione reductase, and concentration of ascorbate and nonprotein thiols.


2021 ◽  
Author(s):  
Δουκάκης Παραδέλλης

Σκοπός: Σκοπός του πειράματος είναι να εκτιμηθεί κατά πόσον η αντιοξειδωτική προετοιμασία με δεφεροξαμίνη μπορεί να ελαττώσει τον τραυματισμό της ισχαιμίας/επαναιμάτωσης του ήπατος που σχετίζεται με εκτεταμένη ηπατεκτομή σε χοίρους.Μέθοδοι: Δεκαοκτώ χοίροι χωρίστηκαν τυχαία σε ομάδες: Δεφεροξαμίνης (DFO) και Χειρουργείου μόνο (SO). Οι χοίροι υποβλήθηκαν σε λαπαροτομία, προσωρινό αποκλεισμό των δεξιών και μέσων ηπατικών αγγείων και ηπατικού πόρου και ακολούθως σε αριστερή ηπατεκτομή. Η ομάδα DFO έλαβε IV δεφεροξαμίνη πριν από την πρόκληση ισχαιμίας του ήπατος. Η παρακολούθηση πραγματοποιήθηκε για 6 ώρες και τα δείγματα (Protein carbonyls (PC), Thiobarbituric acid reactive substances (TBARS), Ιστολογία, ALT, AST, Lactic acid και WBC) συλλέχθηκαν στα 0, 60 και 360 λεπτά.Αποτελέσματα: Οι αντιοξειδωτικοί δείκτες PC και TBARS είχαν σημαντικά χαμηλότερη συγκέντρωση και υψηλότερα ποσοστά μείωσης στον ορό και τον ηπατικό ιστό της ομάδας DFO. Η ιστολογική εξέταση του ήπατος έδειξε λιγότερη φλεγμονή και νέκρωση στην ομάδα DFO. Τα ηπατικά ένζυμα και οι μετρήσεις γαλακτικού οξέος έδειξαν υψηλότερο ρυθμό μείωσης στην ομάδα DFO στο τέλος του πειράματος.Συμπεράσματα: Αυτή η πειραματική μελέτη τεκμηριώνει ένα πρώιμο προστατευτικό αποτέλεσμα της χορήγησης δεφεροξαμίνης σε μείζονες ηπατεκτομές έναντι της βλάβης ισχαιμίας/επαναιμάτωσης στο ήπαρ.


2010 ◽  
Vol 30 (3) ◽  
pp. 199-208 ◽  
Author(s):  
Małgorzata Kujawska ◽  
Ewa Ignatowicz ◽  
Małgorzata Ewertowska ◽  
Jan Oszmiański ◽  
Jadwiga Jodynis-Liebert

Male Wistar rats were treated with chokeberry juice per os, 10 mL/kg/day, for 28 days and a single intraperitoneal (i.p.) dose of N-nitrosodiethylamine (NDEA), 150 mg/kg, or carbon tetrachloride (CCl4), 2 ml/kg. The level of hepatic microsomal lipid peroxidation, expressed as thiobarbituric acid reactive substances (TBARS), was increased in animals dosed with NDEA and CCl4. Juice pretreatment resulted in a significant decrease in TBARS by 53% and 92%, respectively. In rats administered juice alone, 50% decrease in TBARS was noted. The activities of all antioxidant enzymes were decreased in the liver of rats administered either toxicant by 29%—52% as compared to controls. Juice pretreatment resulted in an increase in the activity of catalase, glutathione peroxidase and glutathione reductase by 117%, 56% and 44%, respectively, only in rats challenged with NDEA. Although no response of plasma protein carbonyls to both toxicants was observed, the pretreatment with juice caused a 55% decrease of this parameter in CCl4—dosed rats. DNA damage in blood leukocytes induced by either toxicant was slightly reduced, by 24%, in the rats pretreated with juice and administered NDEA. The results of the study showed that pretreatment with chokeberry juice confers some protection against chemical-induced oxidative stress.


1999 ◽  
Vol 6 (4) ◽  
pp. 452-456 ◽  
Author(s):  
Yutaka Kubota ◽  
Yoshinobu Iwasaki ◽  
Hidehiko Harada ◽  
Ichiro Yokomura ◽  
Mikio Ueda ◽  
...  

ABSTRACT Alveolar macrophages (AMs) are localized in the alveoli and alveolar ducts of the lung and are the only macrophages living in an aerobic environment. Recent studies have demonstrated that AMs play a central role in lung diseases, such as pneumonia and acute respiratory distress syndrome. It has become important to find a simple, effective way to eliminate AMs in order to investigate the function of AMs in vivo. 2-Chloroadenosine (2-CA), a purine analog, is reported to be selectively cytotoxic to cultured macrophages, and we hypothesized that it would deplete the number of AMs in the bronchoalveolar lavage fluid (BALF) of mice without any effect on neutrophil or lymphocyte counts. After mice had inhaled 1 mM aerosolized 2-CA for 2 h, AMs were found to be significantly depleted at 0 h [(4.42 ± 0.16) × 104/ml], 24 h [(4.17 ± 0.89) × 104/ml], 48 h [(3.17 ± 0.21) × 104/ml], and 72 h [(5.00 ± 0.64) × 104/ml] compared with concentrations in untreated controls [(12.1 ± 0.21) × 104/ml]. Neutrophil and lymphocyte counts in BALF did not change and histological changes in the lung were not observed after 2-CA treatment. The lung wet-to-dry weight ratio did not change at 0, 24, and 48 h after 2-CA aerosol application. The 2-CA aerosol had no effect on lung vascular permeability, as assessed by the intravenous administration of Evans blue, or on other phagocytes, as assessed by Kupffer cell counts. Our study demonstrates the efficacy of 2-CA in reducing AM numbers in vivo.


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