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The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.

ABSTRACT: Nitric oxide (NO) and hydrogen sulfide (H₂S) are industrial toxins or pollutants; however, both are produced endogenously and have important biological roles in most mammalian tissues. The recognition that these gasotransmitters have a role in physiological and pathophysiological processes has presented opportunities to harness their intracellular effects either through inhibition of their production; or more commonly, through inducing their levels and or delivering them by various modalities. In this review article, we have focused on an array of NO and H₂S donors, their hybrids with other established classes of drugs, and the various engineered delivery platforms such a fibers, polymers, nanoparticles, hydrogels, and others. In each case, we have reviewed the rationale for their development.

SUBMITTER: Dillon KM

PROVIDER: S-EPMC7263970 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.

Dillon Kearsley M KM Carrazzone Ryan J RJ Matson John B JB Kashfi Khosrow K

Biochemical pharmacology 20200326

Nitric oxide (NO) and hydrogen sulfide (H<sub>2</sub>S) are industrial toxins or pollutants; however, both are produced endogenously and have important biological roles in most mammalian tissues. The recognition that these gasotransmitters have a role in physiological and pathophysiological processes has presented opportunities to harness their intracellular effects either through inhibition of their production; or more commonly, through inducing their levels and or delivering them by various mo ...[more]

PMID: 32224139

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Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of symptoms. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is increasingly associated with cardiovascular complications requiring hospitalizations; however, the mechanisms underlying these complications remain unknown. Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitters that regulate key cardiovascular functions.MethodsBlood samples were obtained from 68 COVID-19 patients and 33 controls and NO and H2S metabolites were assessed. H2S and NO levels were compared between cases and controls in the entire study population and subgroups based on race. The availability of gasotransmitters was examined based on severity and outcome of COVID-19 infection. The performance of H2S and NO levels in predicting COVID-19 infection was also analyzed. Multivariable regression analysis was performed to identify the effects of traditional determinants of gasotransmitters on NO and H2S levels in the patients with COVID-19 infection.ResultsSignificantly reduced NO and H2S levels were observed in both Caucasian and African American COVID-19 patients compared to healthy controls. COVID-19 patients who died had significantly higher NO and H2S levels compared to COVID-19 patients who survived. Receiver-operating characteristic analysis of NO and H2S metabolites in the study population showed free sulfide levels to be highly predictive of COVID-19 infection based on reduced availability. Traditional determinants of gasotransmitters, namely age, race, sex, diabetes, and hypertension had no effect on NO and H2S levels in COVID-19 patients.ConclusionThese observations provide the first insight into the role of NO and H2S in COVID-19 infection, where their low availability may be a result of reduced synthesis secondary to endotheliitis, or increased consumption from scavenging of reactive oxygen species.

Dataset Information

The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.

Publications

The evolving landscape for cellular nitric oxide and hydrogen sulfide delivery systems: A new era of customized medications.

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