Preventive preclinical efficacy of intravenously administered sphingosine-1-phosphate (S1P) in strengthening hypoxia adaptive responses to acute and sub-chronic hypobaric hypoxia

Chawla, Sonam; Rahar, Babita; Tulswani, Rajkumar; Saxena, Shweta

doi:10.1016/j.ejphar.2019.172877

Cited by 13 publications

(6 citation statements)

References 53 publications

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“…Its depletion was associated with COVID-19 cytokine storm, endothelial barrier dysfunction and altered immune response 6,20 . S1P's protective effect on hypoxiainduced oxidative stress and endothelial dysfunction results from its proliferative, anti-apoptotic effects 21 , which forms the rationale for its use as a therapy for hypoxia-related damage 22 . Moreover, the often-observed depletion of Vit.…”

Section: Discussionmentioning

confidence: 99%

Link between serum lipid signature and prognostic factors in COVID-19 patients

Dei

Ottolenghi

Morano

et al. 2021

Sci Rep

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Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including—among others—four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.

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Section: Discussionmentioning

confidence: 99%

Link between serum lipid signature and prognostic factors in COVID-19 patients

Dei

Ottolenghi

Morano

et al. 2021

Sci Rep

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“…In the context of this study, low S1P level in ARDS is a clear sign of lack of adaptation to hypoxia. The slow increase in S1P throughout the hospitalization in parallel to the decrease in inflammatory markers may make S1P a potential drug in hypoxic patients, as recently observed in animal models of hypoxia [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019

Duca

Ottolenghi

Coppola³

et al. 2021

Antioxidants

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In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia. To this purpose, we evaluated a panel of redox state biomarkers that may integrate the routine iron metabolism assays to monitor the patients’ inflammatory and oxidative state. We measured redox and hematopoietic regulators in 20 ARDS patients, 20 ambulatory COPD patients, 9 COVID-19 ARDS-like patients, and 10 age-matched non-hypoxic healthy volunteers (controls). All the examined pathological conditions induced hypoxia, with ARDS and COVID-19 depressing the hematopoietic response without remarkable effects on erythropoietin. Free iron was higher than the controls in all patients, with higher levels of hepcidin and soluble transferrin receptor in ARDS and COVID-19. All markers of the redox state and antioxidant barrier were overexpressed in ARDS and COVID-19. However, glutathionyl hemoglobin, a candidate marker for the redox imbalance, was especially low in ARDS, despite depressed levels of glutathione being present in all patients. Although iron regulation was dysfunctional in all groups, the depressed antioxidant barrier in ARDS, and to a lesser extent in COVID-19, might induce greater inflammatory responses with consequent anemia.

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“…Evidence supports a cardioprotective role of S1P through the S1PRs signaling pathway [61]. Moreover, S1P inhibits oxidative stress and inflammatory responses [62] and positively modulates mitochondrial function, protecting cardiomyocytes from hypoxia/reoxygenation injury (the JAK-STAT pathway and Akt/Gsk3β phosphorylation are likely involved in this event) [63,64].…”

Section: Sphingolipids and Cardiometabolic Riskmentioning

confidence: 90%

Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease

2023

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Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol’s interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.

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Preventive preclinical efficacy of intravenously administered sphingosine-1-phosphate (S1P) in strengthening hypoxia adaptive responses to acute and sub-chronic hypobaric hypoxia

Cited by 13 publications

References 53 publications

Link between serum lipid signature and prognostic factors in COVID-19 patients

Link between serum lipid signature and prognostic factors in COVID-19 patients

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019

Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease

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