Protection by melatonin in respiratory diseases: valuable information for the treatment of COVID-19

2020 ◽  
Vol 3 (3) ◽  
pp. 264-275 ◽  
Author(s):  
Ruediger Hardeland ◽  
Dun-Xian Tan

          High mortality rates in severe progression of COVID-19 are predominantly caused by pulmonary failure due to high-grade airway inflammation. As investigations on the efficacy of melatonin in this disease are still in their beginning, it may be worth-while to recall the body of evidence on protective effects in other respiratory dysfunctions, which have been studied pre-clinically and clinically. In various diseases and corresponding animal models, melatonin has been shown to be protective, mainly because of its anti-inflammatory and antioxidant properties. This was documented in pathologies as different as allergic airway inflammation, toxicologically or radiation-induced acute lung injury, respiratory disorders such as COPD, obstructive sleep apnea, neonatal respiratory distress syndrome, bronchopulmonary dysplasia and asphyxia, impaired respiration in sepsis, idiopathic pulmonary fibrosis, and pulmonary hypertension. The prevailing outcome has been protection or amelioration by melatonin, in conjunction with reduced expression and release of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-8, and TNFα, which was often explained by interference with toll-like receptors, inhibition of NLRP3 inflammasome activation and suppression of NF-κB signaling. In several studies, these beneficial effects were partially related to the upregulation of sirtuin-1 (SIRT1) by melatonin. The body of knowledge on melatonin’s efficacy in respiratory diseases is encouraging for the use of this powerful agent in COVID-19.

2018 ◽  
Vol 53 (4) ◽  
pp. 293-298
Author(s):  
S. Salehi ◽  
MR. Bayatiani ◽  
P. Yaghmaei ◽  
S. Rajabi ◽  
MT. Goodarzi ◽  
...  

Ionizing radiation interacts with biomolecules to produce free radicals, which can damage all components of the cell. The aim of this study was to evaluate the protective effects of different doses of resveratrol against X-ray-induced damage in male rat. The animals were divided into five groups, each composed of six rats: two groups as control groups received saline or ethanol (ethanol in saline, 25%, V/V as a vehicle). Two groups received resveratrol (5 and 10 mg/kg.bwt) for 30 days before X-ray exposure. One group received X-ray. The rats were sacrificed 24 h after the last exposure, blood samples were collected and serum level of malondialdehyde (MDA), total antioxidant capacity (TAC), and the activities of superoxide dismutase (SOD) and catalase (CAT) were measured by spectrophotometric method. X-ray irradiation significantly increased the levels of MDA and decreased TAC as well as SOD activity as compared with control groups. Furthermore, resveratrol pretreatment led to remarkable decrease in MDA concentration and increase in the activities of SOD and CAT as well as TAC compared to those of controls. Our results revealed antioxidant properties of resveratrol and suggest it as a potent radioprotector to ameliorate X-irradiation induced damage in the body.


2010 ◽  
Vol 33 (3) ◽  
pp. 196 ◽  
Author(s):  
Xia Ke ◽  
Jiangju Huang ◽  
Quan Chen ◽  
Suling Hong ◽  
Daoyin Zhu

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma. Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma. Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals. Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.


Author(s):  
Zhidan Li ◽  
Wei Zhang ◽  
Fang Luo ◽  
Jian Li ◽  
Wenbin Yang ◽  
...  

Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post–lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post–lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.


2019 ◽  
Vol 49 (2) ◽  
pp. 284-298 ◽  
Author(s):  
Azadeh Ranjbar Nedamani ◽  
Elham Ranjbar Nedamani ◽  
Azadeh Salimi

Purpose Human health is strongly affected by diet. By the increased use of food industries products, public knowledge about health factors and side effects of chemical additives, the concepts of human health founded an important aspect during past years, and application of natural-based ingredients such as coloring, flavoring, texturizing and anti-oxidative agents was increased. Design/methodology/approach The aim of the present paper is to review the published scientific research studies about lycopene health benefits in different human disease or disorders and bold the necessity of study the health effects of lycopene after its formulation in food industrial products. About 190 papers were searched in Google Scholar, PubMed, Web of Science databases and 72 relevant papers were used. It was found that in medical studies, the lycopene oleoresin or powder is used directly to the subjects. However, it is necessary to study the effectiveness of lycopene in diet food products. Findings According to the literature, it has beneficial effects on cancers, glands, reproductive system, bone, gastric system, liver and fat reduction in the body. Also, it was concluded from the literature that lycopene oxidative cleavages make also its chemo protective effects which is a lost key element to study different food processing on lycopene products or its isomers in final food products and on human health. Originality/value Many ingredients in food formulations are substituted by natural products. Lycopene is a colorant but also, according to the literature, has a strong antioxidative and anti-inflammatory effect to reduce the risk of most important human disease and disorders. Future research in food science can emphasize the effect of different unit operations or formulations on lycopene effects on human health.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rosario Amato ◽  
Maria Grazia Rossino ◽  
Maurizio Cammalleri ◽  
Anna Maria Timperio ◽  
Giuseppina Fanelli ◽  
...  

Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.


Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 325 ◽  
Author(s):  
Ewa Ambrożewicz ◽  
Marta Muszyńska ◽  
Grażyna Tokajuk ◽  
Grzegorz Grynkiewicz ◽  
Neven Žarković ◽  
...  

Hydroxyapatite-based biomaterials are commonly used in surgery to repair bone damage. However, the introduction of biomaterials into the body can cause metabolic alterations, including redox imbalance. Because vitamins D3 and K (K1, MK-4, MK-7) have pronounced osteoinductive, anti-inflammatory, and antioxidant properties, it is suggested that they may reduce the adverse effects of biomaterials. The aim of this study was to investigate the effects of vitamins D3 and K, used alone and in combination, on the redox metabolism of human osteoblasts (hFOB 1.19 cell line) cultured in the presence of hydroxyapatite-based biomaterials (Maxgraft, Cerabone, Apatos, and Gen-Os). Culturing of the osteoblasts in the presence of hydroxyapatite-based biomaterials resulted in oxidative stress manifested by increased production of reactive oxygen species and decrease of glutathione level and glutathione peroxidase activity. Such redox imbalance leads to lipid peroxidation manifested by an increase of 4-hydroxynonenal level, which is known to influence the growth of bone cells. Vitamins D3 and K were shown to help maintain redox balance and prevent lipid peroxidation in osteoblasts cultured with hydroxyapatite-based biomaterials. The strongest effect was observed for the combination of vitamin D3 and MK-7. Moreover, vitamins promoted growth of the osteoblasts, manifested by increased DNA biosynthesis. Therefore, it is suggested that the use of vitamins D3 and K may protect redox balance and support the growth of osteoblasts affected by hydroxyapatite-based biomaterials.


1998 ◽  
Vol 85 (5) ◽  
pp. 1847-1854 ◽  
Author(s):  
Anbo Xiang ◽  
Yoshiyuki Uchida ◽  
Akihiro Nomura ◽  
Hiroaki Iijima ◽  
Fang Dong ◽  
...  

We have developed a guinea pig model for cough related to allergic airway inflammation. Unanesthetized animals were exposed to capsaicin aerosols for 10 min, and cough frequency was counted during this period. The cough evaluation was performed by the following three methods: visual observation, acoustic analysis, and monitoring of pressure changes in the body chamber. These analyses clearly differentiated a cough from a sneeze. To elucidate the relationship between cough response and airway inflammation, animals were immunosensitized and multiple challenged. Sensitized guinea pigs presented no specific changes microscopically, but multiple-challenged animals showed an increased infiltration of inflammatory cells into the airway. Cough number in response to capsaicin increased significantly from 4.7 ± 1.4 coughs/10 min in normal animals to 10.6 ± 2.0 coughs/10 min in sensitized animals and further to 22.8 ± 1.3 coughs/10 min in multiple-challenged animals. This augmented cough frequency was significantly inhibited by the inhalation of tachykinin-receptor antagonists and by oral ingestion, but not inhalation, of codeine phosphate. The results suggest that airway inflammation potentiates an elevation of cough sensitivity in this model.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fangfang Zhao ◽  
Shen Yan ◽  
Mengliang Tian

Weaning causes the generation of excessive reactive oxygen species in the body, which could lead to oxidative stress. Polyphenols, for which blueberries are an important dietary source, are known for various health benefits including antioxidant properties. Here, we sought to elucidate the effects of blueberry polyphenol extracts (BPE) on intestinal antioxidant capacity and possible underlying mechanisms in weaned rats. Ninety-six rats were assigned to two groups and fed either a standard diet or a standard diet supplemented with BPE (200 mg/kg). The results showed that BPE supplementation increased (P < 0.05) catalase and superoxide dismutase activities and decreased (P < 0.05) interleukin-1 and interferon-γ contents in the jejunum and ileum. The abundances of mammalian target of rapamycin, ribosomal p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1 mRNA were elevated in the jejunum and ileum (P < 0.05) after BPE supplementation. Additionally, BPE supplementation decreased (P < 0.05) Kelch-like ECH-associated protein 1 (Keap1) gene transcription and enhanced (P < 0.05) NF-E2-related factor 2 (Nrf2) gene transcription in the jejunum and ileum. According to our results, BPE-induced protective effects against oxidative stress appear through the promotion of the jejunal and ileal antioxidant defense system in weaned rats, which was associated with the Nrf2–Keap1 signaling pathway.


Author(s):  
Cristina Bidian ◽  
Daniela-Rodica Mitrea ◽  
Olivia Gabriela Vasile ◽  
Adriana Filip ◽  
Adriana Florinela Cătoi ◽  
...  

Background. The inflammatory mechanisms occur with the highest prevalence in pulmonary pathology. In pharmaceutical industry, carrageenan is used as a pro-inflammatory agent when the activity of anti-inflammatory agents is tested. The oxidative stress represents the imbalance between pro-oxidants and antioxidants which can lead to the activation of the oxidative mechanisms with noxius potential to the body. In experimental studies, quercetin is the most active flavonoid, having the highest anti-inflammatory and antioxidant effects. Curcumin has antioxidant effects that are similar to those of the standard antioxidants and exerts direct anti-inflammatory activity. Aims. The aim of this study is to determine the antioxidant effects of quercetin and curcumin on a carrageenan-induced pleural inflammation. Methods. Eight groups of adult male rats were used: Ia and Ib -control groups, IIa and IIb -with carrageenan administration, IIIa and IIIb -with curcumin and carrageenan, IVa and IVb -with quercetin and carrageenan administration. Blood and lung samples were taken at 4 hours (Ia, IIa, IIIa, IVa groups) and at 24 hours (Ib, IIb, IIIb, IVb groups) after carrageenan administration. Results. In serum, at 4 and at 24 hours, curcumin and quercetin showed protective effects, reducing the oxidative stress (malondialdehyde significantly decreased) and stimulating the antioxidant protection (ceruloplasmin and glutathione significantly increased) in rats with administration of these substances, in comparison to the group that received only carrageenan. In the lungs, at 4 hours, the oxidative stress was significantly reduced only in the rats that received quercetin (malondialdehyde significantly decreased), modifications that were not observed at 24 hours.     Conclusions. In serum, curcumin presented higher antioxidant effects, compared to quercetin. In lungs, quercetin administration showed superior beneficial effects, but only temporarily.


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