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Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?

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Can early and high intravenous dose of vitamin C prevent and
treat coronavirus disease 2019 (COVID-19)?
Richard Z. Cheng
PII: S2590-0986(20)30015-4
Reference: MEDIDD 100028
To appear in: Medicine in Drug Discovery
Received date: 19 March 2020
Revised date: 23 March 2020
Accepted date: 24 March 2020
Please cite this article as: R.Z. Cheng, Can early and high intravenous dose of vitamin
C prevent and treat coronavirus disease 2019 (COVID-19)?, Medicine in Drug Discovery
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Can early and high intravenous dose of vitamin C prevent and treat
coronavirus disease 2019 (COVID-19)?
Richard Z. Cheng*
Cheng Integrative Health Center, Columbia, SC 29212, U.S.A.
*Corresponding author:
The COVID-19 (SARS-2-Cov) pandemic, first reported in Wuhan, China, is now spreading to
many continents and countries, causing a severe public health burden. Currently, there is no
vaccine or specific antiviral drug for this deadly disease. A quick, deployable and accessible,
effective and safe treatment is urgently needed to save lives and curtail the spreading. Acute
respiratory distress syndrome (ARDS) is a key factor of fatality. Significantly increased
oxidative stress due to rapid release of free radicals and cytokines is the hallmark of ARDS
which leads to cellular injury, organ failure and death. Early use of large dose antioxidants, such
as vitamin C (VC) may become an effective treatment for these patients. Clinical studies also
show that high-dose oral VC provides certain protection against viral infection. Neither
intravenous nor oral administration of high-dose VC is associated with significant side-effects.
Therefore, this regimen should be included in the treatment of COVID-19 and used as a
preventative measure for susceptible populations such as healthcare workers with higher
exposure risks.
Coronaviruses and influenza are among the pandemic viruses that can cause lethal lung
injuries and death from ARDS [1-3]. Viral infections could evoke “cytokine storm” that leads to
lung capillary endothelial cell activation, neutrophil infiltration and increased oxidative stress
(reactive oxygen and nitrogen species). ARDS, characteristic of severe hypoxemia, is usually
accompanied by uncontrolled inflammation, oxidative injury and damage to the alveolar-
capillary barrier [4]. Increased oxidative stress is a major insult in pulmonary injury including
acute lung injury (ALI) and ARDS, two clinical manifestations of acute respiratory failure with
substantially high morbidity and mortality [5,6].
In a report of 29 patients with COVID-19 pneumonia, 27 (93%) showed increased hsCRP, a
marker of inflammation and oxidative stress [7]. Transcription factor, nuclear factor erythroid 2
(nfe2)-related factor 2 (nrf2), is a major regulator of antioxidant response element (ARE)-driven
cytoprotective protein expression. Activation of Nrf2 signaling plays an essential role in
preventing cells and tissues from injury induced by oxidative stress. VC, an important
component of the cellular antioxidant system [8], is beneficial to critical care management [9].
Cytokine storm is observed in both viral and bacterial infections [3] and results in increased
oxidative stress via a common and non-specific pathway. Since the prevention and management
of oxidative stress could be realized by large dose of antioxidants, this approach may be
applicable to COVID-19 with intravenous high-dose VC based on the outcome of three previous
clinical studies involving a total of 146 patients with sepsis [10].
Hemila and colleagues reported that various high-dose intravenous VC infusions (e.g., 200
mg/kg body weight/day, divided into 4 doses) shortened the intensive care unit (ICU) stay by
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97.8% [11], accompanied by a significant reduction in the mortality rate [12]. Such an
experience was reproduced among patients ill with severe influenza [13,14]. Indeed, dietary
antioxidants (VC and sulforaphane) were shown to decrease oxidative stress induced acute
inflammatory lung injury in patients receiving mechanical ventilation [15]. In addition, oral VC
(e.g., 6 g daily) was able to reduce viral infection risk [16] or to improve symptoms [17].
High-dose intravenous VC has also been successfully used in the treatment of 50 moderate
to severe COVID-19 patients in China. The doses used varied between 2 g and 10 g per day,
given over a period of 8 to 10 hours. Additional VC bolus may be required among patients in
critical conditions. The oxygenation index was improving in real time and all the patients
eventually cured and were discharged [18]. In fact, high-dose VC has been clinically used for
several decades and a recent NIH expert panel document states clearly that this regimen (1.5 g/kg
body weight) is safe and without major adverse events [19].
Because the development of efficacious vaccines and antiviral drugs takes time, VC and
other antioxidants are among currently available agents to mitigate COVID-19 associated ARDS.
Given the fact that high-dose VC is safe, healthcare professionals should take a close look at this
opportunity. Obviously, well-designed clinical studies are absolutely needed to develop standard
protocols for bedside use.
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Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-
Infected pneumonia in Wuhan, China. JAMA (2020), 323, 10619.
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Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet (2020), 395, 50713.
3. Fowler III AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, Fisher BJ, Syed A, DeWilde
C, Priday A, Kasirajan V. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus
induced acute respiratory distress syndrome. World J Crit Care Med (2017), 6, 8590.
4. Meng L, Zhao X, Zhang H. HIPK1 Interference attenuates inflammation and oxidative stress of
acute lung injury via autophagy. Med Sci Monit (2019), 25, 82735.
5. Yan X, Fu X, Jia Y, Ma X, Tao J, Yang T, Ma H, Liang X, Liu X, Yang J, Wei J. Nrf2/Keap1/ARE
signaling mediated an antioxidative protection of human placental mesenchymal stem cells of fetal
origin in alveolar epithelial cells. Oxid Med Cell Longev (2019), 2019:2654910.
6. Hecker L. Mechanisms and consequences of oxidative stress in lung disease: therapeutic
implications for an aging populace. Am J Physiol Lung Cell Mol Physiol (2018), 314, L64253.
7. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, Deng Y, Wei S. Analysis of clinical features of 29
patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi (2020), 43,
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8. Liu Q, Gao Y, Ci X. Role of Nrf2 and its activators in respiratory diseases. Oxid Med Cell Longev
(2019), 2019:7090534.
9. Nabzdyk CS, Bittner EA. Vitamin C in the critically ill - indications and controversies. World J Crit
Care Med (2018), 7, 5261.
10. Li J. Evidence is stronger than you think: a meta-analysis of vitamin C use in patients with sepsis.
Crit Care (2018), 22, 258.
11. Hemilä H, Chalker E. Vitamin C can shorten the length of stay in the ICU: a meta-analysis.
Nutrients (2019), 11, 708.
12. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and
thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study.
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13. High dose vitamin C and influenza: a case report. ISOM, cited on Feb 9 2020
14. Levy T. Primal Panacea. MedFox Publishing; 350 p. (Kindle Edition).
15. Patel V, Dial K, Wu J, Gauthier AG, Wu W, Lin M, Espey MG, Thomas DD, Jr CRA, Mantell LL.
Dietary antioxidants significantly attenuate hyperoxia-induced acute inflammatory lung injury by
enhancing macrophage function via reducing the accumulation of airway HMGB1. Int J Mol Sci
(2020), 21, 977.
16. Kim TK, Lim HR, Byun JS. Vitamin C supplementation reduces the odds of developing a common
cold in Republic of Korea Army recruits: randomised controlled trial. BMJ Mil Health (2020), DOI:
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18. Shanghai Expert Panel, cited on Mar 23, 2020
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9 2020 (
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... It is known that high-dose VC provides a certain protection against viral infection. Intravenous VC may also attenuate the cytokine storm in the COVID-19 infection besides its antiviral properties (7). High-dose vitamin C is an example of a substance that has proven to alter blood glucose measurements on glucose devices. ...
... Currently, no suitable vaccine or specific antivirals are available for COVID-19. Acute respiratory distress syndrome (ARDS) is considered as the virtual reason for mortality (7). Coronaviruses may lead to significant lung damage and death from ARDS via the activation of pulmonary capillary endothelium, infiltration by neutrophils, and enhanced oxidative stress as a result of "cytokine storm" (3,4). ...
... The oxidization of ascorbic acid at the electrode surface, leading to more electrons and current production, which leads to a false increase in blood glucose reading (5). The antiviral activities of VC were known for decades and high-dose intravenous VC treatment was shown to be effective in patients with sepsis, ill with severe influenza, receiving mechanical ventilation (7). In addition to direct antiviral properties, intravenous VC may also attenuate the cytokine storm in the COVID-19 infection. ...
... It's an antioxidant that keeps the intracellular reductive-oxidative homeostasis [29] . The increased oxidative stress in COVID-19 patients caused by free radicals and cytokine's rapid release during a cytokine storm makes an urgent need to add antioxidants in the treatment protocols for COVID-19, vitamin C is the most suggested antioxidant [30] . ...
... Staying in the intensive care unit (ICU) decreased by 7.8% after 200 mg/kg body weight/day consumption [31]. Some studies have shown that oral vitamin C decreases the risk of infection with viruses [30] . Analysis of 17 COVID-19 patients found that the use of high-dose I.V. Vitamin C can be used in patients with moderate-severe illnesses [31] . ...
... Hasta la fecha, no existe consenso ni eficacia probada de la suplementación con ácido ascórbico en pacientes con COVID-19, pero algunos investigadores recomiendan un posible uso de suplementación IV, como se indica en un documento del panel de expertos del Instituto Nacional de Cáncer del Instituto Nacional de Salud de Estados Unidos, en el que se menciona que una dosis de 1,5 g/kg de peso corporal podría considerarse seguro y sin efectos adversos importantes (29) . Otros autores no hacen recomendaciones para la prevención de infecciones virales y recomiendan para el tratamiento 1 g/día (12) . ...
Las opciones terapéuticas en el manejo de coronavirus disease 2019 (COVID-19) son limitadas y el proceso de vacunación para proteger contra el contagio del coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) está iniciando en el mundo. A todo esto, hay que añadir la existencia de un grupo de personas que presentan mayor vulnerabilidad frente a la enfermedad, como son los adultos mayores y las personas con enfermedades crónicas como la obesidad, la diabetes y la hipertensión arterial. Además, los trastornos en el estado nutricional pueden influir en el curso de la enfermedad. Las vitaminas y los oligoelementos desempeñan un papel crucial en la inmunomodulación, por lo que se han postulado como una opción terapéutica. El objetivo de este artículo es mostrar el papel de los micronutrientes en la inmunidad y, en particular, la evidencia actual sobre los efectos de su suplementación en la prevención y el tratamiento de la infección por SARS-CoV-2. La revisión de la literatura muestra que en la actualidad no existen estudios suficientes sobre los beneficios de la suplementación de micronutrientes en el curso de la COVID-19. Una dieta equilibrada y variada es esencial no solo para minimizar las deficiencias de vitaminas, sino también para evitar un consumo excesivo o suplementación innecesaria. Se requieren de estudios aleatorizados controlado que estudien los efectos de la suplementación con micronutrientes en la función inmunitaria y en los resultados clínicos en diferentes poblaciones. Palabras clave: inmunidad, vitaminas, minerales, obesidad, infecciones por coronavirus, SARS-CoV-2.
... The world outbreak mortality rate is about 3%, and frail patients who had comorbidities such as cardiovascular disease, diabetes, asthma, etc. are at high risk (Pascarella et al., 2020). Both the influenza virus and the coronavirus are deadly respiratory tract infections that cause mortality from acute respiratory distress syndrome (ARDS) (Cheng, 2020). ...
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Objective: Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) affects millions of people worldwide. The article aims to review the therapeutic perspective on natural antioxidants, their mechanism of action, pharmacokinetics in management and cure of COVID‐19/ SARS‐CoV‐2 infection. Methods: We conducted a literature search including World Health Organization and National Institute of Health guidelines and clinical trials registered with limited to antioxidants in COVID‐19 management. Results: Elderly, immunocompromised patients, and others with underlying health conditions or multiple comorbidities have a high mortality rate. Disrupted redox homeostasis and oxidative stress seem to be biological pathways that may increase personal vulnerability to infection. Antioxidants like vitamins C, D, E, epigallocatechin‐3 gallate, and morin have been reported to protect against COVID‐19 disease. Reactive oxygen species are immunological regulatory elements of viral replication. Natural antioxidants exhibit potential action in preventing inflammation and organ dysfunction during viral infection. They also increase glutathione level, oxygenation rate, and immunological responses in the treatment of sepsis and acute respiratory distress syndrome. Conclusion: No wonder the selection of prevention, treatment, and cure of COVID‐19 and SARS‐CoV‐2 mainly depends upon the antiviral and immunoregulatory activity which they possess. Yet, their efficacy against COVID‐19 is of great concern and demands extensive study. Transmission of Covid‐19 from host to community and its prevention and treatment using natural anti‐oxidants
... Vitamin C has been demonstrated to increase neutrophil migration to the infection site, triggering the production of reactive oxygen species (ROS) and phagocytosis (Carr & Maggini, 2017;Carr & Melcher, 2017). A clinical trial among 50 COVID cases was performed, in which high-dose vitamin C intravenous intervention was given and outcomes have shown positive changes in the oxygenation index of COVID patients (Cheng, 2020). ...
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The Coronavirus disease 2019 (COVID‐19) has spread across the globe and is causing widespread disaster. The impact of gut microbiota on lung disease has been widely documented. Diet, environment, and genetics all play a role in shaping the gut microbiota, which can influence the immune system. Improving the gut microbiota profile through customized diet, nutrition, and supplementation has been shown to boost immunity, which could be one of the preventative methods for reducing the impact of various diseases. Poor nutritional status is frequently linked to inflammation and oxidative stress, both of which can affect the immune system. This review emphasizes the necessity of maintaining an adequate level of important nutrients to effectively minimize inflammation and oxidative stress, moreover to strengthen the immune system during the COVID‐19 severity. Furthermore, the purpose of this review is to present information and viewpoints on the use of probiotics, prebiotics, and synbiotics as adjuvants for microbiota modification and its effects on COVID‐19 prevention and treatment. This review emphasizes the necessity of maintaining an adequate level of important nutrients to effectively minimize inflammation and oxidative stress, and also to strengthen the immune system during the COVID‐19 severity.
... It has been reported that vitamin C supplementation is protective against viral infections as it strengthens a person's immunity. In a study conducted in China, in addition to the treatment of patients with moderate and severe COVID-19, high doses of vitamin C (10-20g/day, 8-10 hours) were administered to 50 patients and found to be successful in treating the virus [13]. In our study, the increase in vitamin C consumption by resident physicians during the pandemic was found to be 75.2%. ...
... 17 Various viral infections such as sepsis, sepsis-related acute respiratory disease syndrome (ARDS), and other common ailments have been linked to lower vitamin C levels. 18 As vitamin C inhibits viral growth when present in sufficient quantities in vitro, the elevated levels may have virucidal effects. 19 In a study conducted by Li et al., it was shown that influenza-infected mice were unable to produce vitamin C, and then the mice which didn't receive vitamin C supplements had higher lung pathology scores. ...
... Even though the benefi ts of vitamin C for the body are widely known, the coronavirus infection is new wherefore there are yet not enough relevant scientifi c studies to confi rm the effect of taking vitamin C-containing products during COVID-19. There are even cases of acute renal insuffi ciency caused by high doses of vitamin C (27,28). ...
Our body senses two types of pain, acute and chronic. Acute pain lasts for a short time. It occurs when our body wants to protect us from a dangerous situation. This way, our nerves are telling us that something is wrong. But if some time passes since our injury, treatment or surgery and the pain or discomfort persists, we are speaking of chronic pain. It is often difficult to determine its intensity or even prove its existence. The discomfort and pain are not relieved and physical pain may be accompanied by mental issues. At present, during the COVID-19 pandemic, chronic pain is becoming more prominent, and it is also associated with the post-COVID syndrome. In their efforts to help patients suffering from COVID-19, many new treatment protocols have been prepared and various antiviral drugs and other potentially useful drugs have been used (often without prior approval or testing). Basically, it was a kind of 'experimental' treatment. At present, thanks to quick therapy decisions and as part of COVID-19 prevention, we have succeeded in stabilising the situation all over the world. A relatively fast development of vaccines against SARS-CoV-2 with a view to achieve collective immunity has greatly contributed to this. On the other hand, 'quick decisions' have contributed to other significant issues which we are beginning to deal with now, i.e, in the effort to defeat the virus, many experts regarded the adverse effects of the medications used to be of secondary importance. In the article we would like to point out the other side of the 'successful' treatment of COVID-19, namely the possible iatrogenic conditions which significantly contribute to the post-COVID‑19 syndrome and chronic pain. The importance of preventive measures over uncertain result of COVID-19 treatment is emphasised (Tab. 4, Fig. 1, Ref. 50). Text in PDF Keywords: iatrogenic conditions; chronic pain; co-morbidity; pain syndrome; pandemic; post-COVID‑19 syndrome.
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Background: The aim of the present study was to analyze any relations existed between sampling characteristics and the onset of the SARS-CoV-2 infection, also by considering the number of times that it occurred in a cohort of Italian nurses interviewed. Additionally, by considering the nutritional supplemental taking, this research wanted to assess any differences both in the onset and in the number of times which the infection occurred among participants. Method: An observational cohort study was carried out thorough all Italian nurses by advertising the questionnaire through some professional internet pages. Results: Work typology (p=0.021), ward Covid-19 (p=0.002) and regular meal assumption (p=0.019) significantly associated to the onset of the SARS-CoV-2 infection. Most of nurses who contracted the SARS-CoV-2 infection worked during the night shift (53.7%), 44.3% worked in a no-Covid-19 ward and 53% declared to have a regular meals’ assumption. Ward typology significantly associated to the times of the SARS-CoV-2 onset (p=0.003), as most of nurses who contracted almost one time the SARS-CoV-2 infection were employed in a no-Covid-19 ward (55.5%) and 54.1% of them declared to have a regular meals’ assumption. The onset of the Sars-CoV-2 infection seemed to be more present in the most part of the sample collect. Conclusion: The present study could be considered as pilot in this sense and also more studies will be performed in order to better relate the function of supplemental food intakes with a better functioning of the immune system.
The novel coronavirus, now known as COVID-19, was first reported in China in December 2019 and became a global crisis by March 2020. Both adaptive and maladaptive behaviours were observed in response to aspects of the crisis, some of which appeared to be contradictory to coping and curbing the threat of COVID-19. For instance, the purchase and use of surgical masks and sanitisers could be understood as logical health-oriented behaviours relevant to coping with the COVID-19 pandemic. The breaching of social distancing measures and forwarding unverified news, however, might have done more harm than good. In applying the proximal and distal defences proposed within the Terror Management Health Model (TMHM), this article suggests explanations for these behaviours as individuals’ attempts to alleviate anxiety arising from reminders of their mortality. Information from local newspapers and media is used to highlight and identify common behaviours observed in the pandemic, and the TMHM is applied to explain these behaviours. This paper briefly concludes with a call for empirical validation of the TMHM for the behaviours observed in relation to COVID-19, and for the use of TMHM conceptualisations to develop countermeasures to reduce maladaptive behaviours in the current, and future, pandemics in Singapore.
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Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation.
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The oxidative stresses are a major insult in pulmonary injury such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality. Mesenchymal stem cells (MSCs) hold a promise in treatments of many human diseases, mainly owing to their capacities of immunoregulation and antioxidative activity. The strong immunoregulatory role of human placental MSCs of fetal origin (hfPMSCs) has been previously demonstrated; their antioxidant activity, however, has yet been interrogated. In this report, we examined the antioxidative activity of hfPMSCs by accessing the ability to scavenge oxidants and radicals and to protect alveolar epithelial cells from antioxidative injury using both a cell coculture model and a conditioned culture medium (CM) of hfPMSCs. Results showed a comparable antioxidative capacity of the CM with 100 μ M of vitamin C (VC) in terms of the total antioxidant capacity (T-AOC), scavenging abilities of free radicals DPPH, hydroxyl radical (·OH), and superoxide anion radical (O 2⁻ ), as well as activities of antioxidant enzymes of SOD and GSH-PX. Importantly, both of the CM alone and cocultures of hfPMSCs displayed a protection of A549 alveolar epithelial cells from oxidative injury of 600 μ M hydrogen peroxide (H 2 O 2 ) exposure, as determined in monolayer and transwell coculture models, respectively. Mechanistically, hfPMSCs and their CM could significantly reduce the apoptotic cell fraction of alveolar epithelial A549 cells exposed to H 2 O 2 , accompanied with an increased expression of antiapoptotic proteins Bcl-2, Mcl-1, Nrf-2, and HO-1 and decreased proapoptotic proteins Bax, caspase 3, and Keap1, in comparison with naïve controls. Furthermore, hfPMSCs-CM (passage 3) collected from cultures exposed an inhibition of the Nrf2/Keap1/ARE signaling pathway which led to a significant reduction in caspase 3 expression in A549 cells, although the addition of Nrf2 inhibitor ML385 had no effect on the antioxidative activity of hfPMSCs-CM. These data clearly suggested that hfPMSCs protected the H 2 O 2 -induced cell oxidative injury at least in part by regulating the Nrf2-Keap1-ARE signaling-mediated cell apoptosis. Our study thus provided a new insight into the antioxidative mechanism and novel functions of hfPMSCs as antioxidants in disease treatments, which is warranted for further investigations.
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A number of controlled trials have previously found that in some contexts, vitamin C can have beneficial effects on blood pressure, infections, bronchoconstriction, atrial fibrillation, and acute kidney injury. However, the practical significance of these effects is not clear. The purpose of this meta-analysis was to evaluate whether vitamin C has an effect on the practical outcomes: length of stay in the intensive care unit (ICU) and duration of mechanical ventilation. We identified 18 relevant controlled trials with a total of 2004 patients, 13 of which investigated patients undergoing elective cardiac surgery. We carried out the meta-analysis using the inverse variance, fixed effect options, using the ratio of means scale. In 12 trials with 1766 patients, vitamin C reduced the length of ICU stay on average by 7.8% (95% CI: 4.2% to 11.2%; p = 0.00003). In six trials, orally administered vitamin C in doses of 1–3 g/day (weighted mean 2.0 g/day) reduced the length of ICU stay by 8.6% (p = 0.003). In three trials in which patients needed mechanical ventilation for over 24 hours, vitamin C shortened the duration of mechanical ventilation by 18.2% (95% CI 7.7% to 27%; p = 0.001). Given the insignificant cost of vitamin C, even an 8% reduction in ICU stay is worth exploring. The effects of vitamin C on ICU patients should be investigated in more detail.
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strong>BACKGROUND Acute respiratory distress syndrome (ARDS), which is characterized by severe hypoxemia (PaO2/FIO2 ≤300 mmHg), is usually companied by uncontrolled inflammation, oxidative injury, and the damage to the alveolar-capillary barrier. Severe ARDS is usually companied with acute lung injury that worsen the patients' condition. HIPK1 is a modulator of homeodomain-containing transcription factors and regulates multiple cellular biological process associated with inflammation and anti-stress responses. MATERIAL AND METHODS We used an LPS-induced mouse acute lung injury (ALI) model to investigate the possible role of HIPK1 in ALI pathophysiology. RESULTS We found the HIPK1 was elevated in ALI model mice while interference of HIPK1 by siRNA attenuated the inflammation and oxidative stress indicators (H2O2, O-2, and NO). Further research found HIPK1 interference enhanced the autophagy. CONCLUSIONS Decreased HIPK1 in ALI showed protective effects in attenuating inflammation and oxidative stress and enhancing autophagy, indicating HIPK1 as a possible target in ALI management.
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Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant response element- (ARE-) driven cytoprotective protein expression. The activation of Nrf2 signaling plays an essential role in preventing cells and tissues from injury induced by oxidative stress. Under the unstressed conditions, natural inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), traps Nrf2 in the cytoplasm and promotes the degradation of Nrf2 by the 26S proteasome. Nevertheless, stresses including highly oxidative microenvironments, impair the ability of Keap1 to target Nrf2 for ubiquitination and degradation, and induce newly synthesized Nrf2 to translocate to the nucleus to bind with ARE. Due to constant exposure to external environments, including diverse pollutants and other oxidants, the redox balance maintained by Nrf2 is fairly important to the airways. To date, researchers have discovered that Nrf2 deletion results in high susceptibility and severity of insults in various models of respiratory diseases, including bronchopulmonary dysplasia (BPD), respiratory infections, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and lung cancer. Conversely, Nrf2 activation confers protective effects on these lung disorders. In the present review, we summarize Nrf2 involvement in the pathogenesis of the above respiratory diseases that have been identified by experimental models and human studies and describe the protective effects of Nrf2 inducers on these diseases.
Introduction The Republic of Korea (ROK) military has a high incidence of respiratory diseases at training centres. Vitamin C has been reported to reduce the incidence of colds. For the purpose of preventing soldiers' respiratory diseases, this study aimed to investigate whether vitamin C intake can prevent common colds in the ROK Army soldiers. Methods This was a randomised, placebo-controlled, and double-blind trial of soldiers who enlisted in the Korea Army Training Centre for 30 days from 12 February to 13 March 2018. The study participants were divided into groups (vitamin C vs placebo). The military medical records were searched to determine whether the participants had a common cold. Multiple logistic regression analysis was performed to identify the association between vitamin C intake and diagnosis of common colds. In addition, subgroup analysis on the relationship between vitamin C intake and common cold according to smoking status, training camp and physical rank was conducted. Results A total of 1444 participants were included in our study. Of these participants, 695 received vitamin C (6000 mg/day, vitamin C group), while 749 participants received placebo (0 mg/day, placebo group). The vitamin C group had a 0.80-fold lower risk of getting a common cold than did the placebo group. Subgroup analyses showed that this effect was stronger among subjects in camp A, among never smokers and among those in physical rank 3. Conclusion Vitamin C intake provides evidence to suggest that reducing the common colds in Korean Army soldiers. Our results may serve as a basis for introducing military healthcare policies that can provide vitamin C supplementation for military personnel in basic military training.
Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.
Background: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding: National Key R&D Program of China.