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 12 publications

(4 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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“…Additionally, sphingosine-1-phosphate and sphinganine-1-phosphate levels were upregulated by high altitude exposure. Sphingosine-1-phosphate has been reported to confer adaptive and protective advantages against hypobaric hypoxia during acute or sub-chronic phases [29]. Plasma taurine (2-aminoethanesulfonic acid) levels also showed a significant increase at high altitude, which also has been shown to have protective effects against hypoxia [30,31].…”

Section: Characteristics Of Plasma Metabolome and Clinical Indicesmentioning

confidence: 99%

Longitudinal multi-omics analysis uncovers the altered landscape of gut microbiota and plasma metabolome in response to high altitude

Han,

Liu,

Jia

et al. 2024

Microbiome

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Background Gut microbiota is significantly influenced by altitude. However, the dynamics of gut microbiota in relation to altitude remains undisclosed. Methods In this study, we investigated the microbiome profile of 610 healthy young men from three different places in China, grouped by altitude, duration of residence, and ethnicity. We conducted widely targeted metabolomic profiling and clinical testing to explore metabolic characteristics. Results Our findings revealed that as the Han individuals migrated from low altitude to high latitude, the gut microbiota gradually converged towards that of the Tibetan populations but reversed upon returning to lower altitude. Across different cohorts, we identified 51 species specifically enriched during acclimatization and 57 species enriched during deacclimatization to high altitude. Notably, Prevotella copri was found to be the most enriched taxon in both Tibetan and Han populations after ascending to high altitude. Furthermore, significant variations in host plasma metabolome and clinical indices at high altitude could be largely explained by changes in gut microbiota composition. Similar to Tibetans, 41 plasma metabolites, such as lactic acid, sphingosine-1-phosphate, taurine, and inositol, were significantly elevated in Han populations after ascending to high altitude. Germ-free animal experiments demonstrated that certain species, such as Escherichia coli and Klebsiella pneumoniae, which exhibited altitude-dependent variations in human populations, might play crucial roles in host purine metabolism. Conclusions This study provides insights into the dynamics of gut microbiota and host plasma metabolome with respect to altitude changes, indicating that their dynamics may have implications for host health at high altitude and contribute to host adaptation.

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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 12 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

Longitudinal multi-omics analysis uncovers the altered landscape of gut microbiota and plasma metabolome in response to high altitude

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