Hydrogen Sulfide in Exhaled Gases From Ventilated Septic Neonates and Children: A Preliminary Report

Bee, Natalie; White, Ruth Rennicks; Petros, Andy

doi:10.1097/pcc.0000000000001223

Cited by 12 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serum H 2 S level in each group was measured in the present study. The level of endogenous H 2 S in the serum of rats appeared to increase following CLP, which was consistent with the findings of Bee et al (34). This phenomenon may be associated with the upregulation of inducible nitric oxide synthase (iNOS) expression during septic shock.…”

Section: Discussionsupporting

confidence: 92%

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

Liu

Tian

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H 2 S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H 2 S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H 2 S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H 2 S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H 2 S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H 2 S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H 2 S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H 2 S. Additionally, H 2 S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H 2 S. In conclusion, the results of the current study suggest that exogenous H 2 S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.

show abstract

Section: Discussionsupporting

confidence: 92%

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

Liu

Tian

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…H 2 S has a great potential to act as a prognostic marker of septic shock and its severity level becomes higher in septic patients within 12 hours of onset of sepsis 294,295. Even H 2 S can be detected in the exhaled pulmonary gases of patients with sepsis 296. Thus, H 2 S negatively regulates NLRP3 at all concentrations, but increases the proinflammatory action of NLRP1b inflammasome at its higher level, aggravating the sepsis-associated organ damage.…”

Section: Inflammasomes In the Immunopathogenesis Of Sepsismentioning

confidence: 99%

Inflammasomes: Pandora’s box for sepsis

Kumar

2018

JIR

View full text Add to dashboard Cite

Sepsis was known to ancient Greeks since the time of great physician Hippocrates (460–377 BC) without exact information regarding its pathogenesis. With time and medical advances, it is now considered as a condition associated with organ dysfunction occurring in the presence of systemic infection as a result of dysregulation of the immune response. Still with this advancement, we are struggling for the development of target-based therapeutic approach for the management of sepsis. The advancement in understanding the immune system and its working has led to novel discoveries in the last 50 years, including different pattern recognition receptors. Inflammasomes are also part of these novel discoveries in the field of immunology which are <20 years old in terms of their first identification. They serve as important cytosolic pattern recognition receptors required for recognizing cytosolic pathogens, and their pathogen-associated molecular patterns play an important role in the pathogenesis of sepsis. The activation of both canonical and non-canonical inflammasome signaling pathways is involved in mounting a proinflammatory immune response via regulating the generation of IL-1β, IL-18, IL-33 cytokines and pyroptosis. In addition to pathogens and their pathogen-associated molecular patterns, death/damage-associated molecular patterns and other proinflammatory molecules involved in the pathogenesis of sepsis affect inflammasomes and vice versa. Thus, the present review is mainly focused on the inflammasomes, their role in the regulation of immune response associated with sepsis, and their targeting as a novel therapeutic approach.

show abstract

“…This may be part of the physiological elimination process, but, more importantly, increased H 2 S levels in exhaled air have been demonstrated when animals or human volunteers were subjected to therapeutic doses of H 2 S donors (Insko et al, 2009;Toombs et al, 2010). Increased exhaled H 2 S has been demonstrated in asthmatic patients (Zhang et al, , 2015 and in septic patients (Bee et al, 2017). Exhaled H 2 S measurements may be one potential future way to monitor exposure to H 2 S donating agents, with one of its benefits being the ability to obtain an immediate read-out (as opposed to methods using H 2 S derivatization of blood or plasma and subsequent biochemical detection).…”

Section: H 2 S Delivery Via Inhalation Of H 2 S Gasmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

2017

View full text Add to dashboard Cite

Over the last decade, hydrogen sulfide (HS) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, HS is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. HS levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of HS, either based on HS donation or inhibition of HS biosynthesis. HS donation can be achieved through the inhalation of HS gas and/or the parenteral or enteral administration of so-called fast-releasing HS donors (salts of HS such as NaHS and NaS) or slow-releasing HS donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated HS release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with HS-donating groups (the most advanced compound in clinical trials is ATB-346, an HS-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of HS synthesis, there are now several small molecule compounds targeting each of the three HS-producing enzymes cystathionine--synthase (CBS), cystathionine--lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous HS production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known HS donors and HS biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.

show abstract

Hydrogen Sulfide in Exhaled Gases From Ventilated Septic Neonates and Children: A Preliminary Report

Abstract: Hydrogen sulfide can be detected in expired pulmonary gases in very low concentrations of parts per billion. Significantly higher levels are seen in septic patients compared with controls. The pattern of response was similar to that of C-reactive protein.

Cited by 12 publications

References 31 publications

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

Inflammasomes: Pandora’s box for sepsis

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors

Contact Info

Product

Resources

About

Hydrogen Sulfide in Exhaled Gases From Ventilated Septic Neonates and Children: A Preliminary Report

Abstract: Hydrogen sulfide can be detected in expired pulmonary gases in very low concentrations of parts per billion. Significantly higher levels are seen in septic patients compared with controls. The pattern of response was similar to that of C-reactive protein.

Cited by 12 publications

References 31 publications

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

H2S attenuates sepsis‑induced cardiac dysfunction via a PI3K/Akt‑dependent mechanism

Inflammasomes: Pandora&rsquo;s box for sepsis

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

Contact Info

Product

Resources

About

Inflammasomes: Pandora’s box for sepsis

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H₂S Levels: H₂S Donors and H₂S Biosynthesis Inhibitors