New Insights into the Role of Glutathione in the Mechanism of Fever

Wrotek, Sylwia; Sobocińska, Justyna; Kozłowski, Henryk M; Pawlikowska, Małgorzata; Jędrzejewski, Tomasz; Dzialuk, Artur

doi:10.3390/ijms21041393

Cited by 26 publications

(23 citation statements)

References 119 publications

(161 reference statements)

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“…19 It is noteworthy that GSH not only affects certain factors involved in immunological processes, but it also modifies complex immune reactions such as fever, and there are data suggesting that fever induction is associated with oxidative stress. 20 Although the complement system is a key mediator of the innate immune response that protects against infectious agents, it also plays a critical role in promoting the inflammatory process that leads to tissue injury. 21 In particular, complement may be involved in coronavirus pathogenesis, as inferred from the finding that C3 knockout mice infected with SARS-CoV have less lung disease than wild-type mice.…”

Section: F I G U R Ementioning

confidence: 99%

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Balansky²,

2020

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COVID‐19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokine storm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID‐19 patients. N‐ Acetyl‐L‐cysteine (NAC) is a precursor of reduced glutathione (GSH). Due to its tolerability, this pleiotropic drug has been proposed not only as a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving GSH depletion and oxidative stress. At very high doses, NAC is also used as an antidote against paracetamol intoxication. Thiols block the angiotensin‐converting enzyme 2 thereby hampering penetration of SARS‐CoV‐2 into cells. Based on a broad range of antioxidant and anti‐inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID‐19, as it was previously demonstrated for influenza and influenza‐like illnesses. Moreover, high‐dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID‐19 cases and in the control of its lethal complications, also including pulmonary and cardiovascular adverse events.

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Section: F I G U R Ementioning

confidence: 99%

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Balansky²,

2020

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“…Thus, depleted endogenous GSH could be the cause of inflammation in stressed rats. Although GSH prevents the production of most inflammatory cytokines, it is also needed to maintain an adequate interferon gamma production, which is essential for the host defense ( 47 , 48 ). Cells maintain a high vitamin C concentration especially in leucocytes, eyes, the adrenal and pituitary glands, and the brain ( 49 ), while infection and stress reduces the levels of both vitamin C and zinc ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Possible Prophylactic Approach for SARS-CoV-2 Infection by Combination of Melatonin, Vitamin C and Zinc in Animals

et al. 2020

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SARS-CoV-2, an epidemic, causes severe stress in both human and animals and may induce oxidative stress (OS) and increases susceptibility to infection. Domestic animals are found infected by their COVID-2 suffering owners. Chronic immobilization stress (CIS), a model of psychological and physical stress of confinement, can trigger depression and anxiety in animals. We evaluated the ameliorative effect of the proposed SARS-CoV-2 prophylactic drugs melatonin, vitamin C, and zinc on CIS-induced OS, inflammation, and DNA damage in rats. Forty male Swiss albino rats (200–250 g, 7–9 weeks old) were divided into five groups as controls, CIS, treated with melatonin (20 mg/kg), and vitamin C plus zinc [VitC+Zn (250 + 2.5 mg/kg)] alone or in combination (melatonin+VitC+zinc) subjected to CIS for 3 weeks. CIS was induced by immobilizing the whole body of the rats in wire mesh cages of their size with free movement of head. Exposure to CIS significantly compromised the circulatory activities of superoxide dismutase, catalase, and glutathione with enhanced malondialdehyde, inflammatory markers (IL-6, IL10, and TNFα), and lymphocyte DNA damage in comparison to controls. Treatment with melatonin and VitC+Zn alone or in combination significantly restored the altered biochemical parameters and DNA damage of stressed rats to their respective control values. However, the cumulative action of melatonin with VitC+Zn was more effective in alleviating the CIS-induced OS, inflammation, and DNA damage. The present study indicates that the antioxidant combination can be an effective preventive measure to combat severe psychological and confinement stress-induced biochemical changes in animals due to abnormal conditions such as SARS-CoV-2.

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“…Glutathione biosynthesis is critical for the correct endothelia function and in anti‐fibrotic responses 46 . A close relationship between GSH homeostasis and fever has been reported recently, assessing that the role of GSH in the febrile response to inflammation and the role of fever on GSH availability and biosynthesis are closely intertwined 47 …”

Section: Fever As An Early Symptom Of Covid‐19 Acetaminophen Should N...mentioning

confidence: 98%

Home pharmacological therapy in early COVID‐19 to prevent hospitalization and reduce mortality: Time for a suitable proposal

Pandolfi

Chirumbolo

Ricevuti

et al. 2021

Basic Clin Pharma Tox

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The COVID-19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post-mortem autopsy was performed on a very modest number of patients who died from COVID-19 infection, leading to a first confirmation of an immune-thrombosis of the lungs as the major COVID-19 pathogenesis, likewise for SARS. Since then (June-August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti-inflammatory, anti-platelet, anticoagulant and antibiotic therapy confirmed that COVID-19 was an endothelial inflammation with immuno-thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immunethrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti-inflammatory therapy may treat endothelia inflammation and immune-thrombosis caused by COVID-19, by using drugs we are going to recommend in this paper.

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New Insights into the Role of Glutathione in the Mechanism of Fever

Cited by 26 publications

References 119 publications

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Rationale for the use of N ‐acetylcysteine in both prevention and adjuvant therapy of COVID‐19

Possible Prophylactic Approach for SARS-CoV-2 Infection by Combination of Melatonin, Vitamin C and Zinc in Animals

Home pharmacological therapy in early COVID‐19 to prevent hospitalization and reduce mortality: Time for a suitable proposal

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