The effect of a hydrogen sulfide releasing molecule (Na2S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model

Balaban, Cecilia Lucía; Rodriguez, Joaquı́n V.; Tiribelli, Claudio; Guibert, Edgardo E.

doi:10.1016/j.cryobiol.2015.06.006

Cited by 15 publications

(8 citation statements)

References 36 publications

(42 reference statements)

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“…One such effort focuses on induction of reversible metabolic suppression ("hibernation"), most reproducibly achieved in mice and small rodents, to cope with the reduced oxygen availability to the tissues, for example, during lethal hypoxia or after severe blood loss (Blackstone et al, 2005;Blackstone and Roth, 2007;Aslami et al, 2009). Another application of the same concept may be the "on-demand," reversible metabolic suppression of stored organs in an attempt to extend their storage life (Balaban et al, 2015;Lobb et al, 2015).…”

Section: The Modes Of H 2 S's Biologic Actionsmentioning

confidence: 99%

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

2017

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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.

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Section: The Modes Of H 2 S's Biologic Actionsmentioning

confidence: 99%

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

2017

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“…(ii) Another strategy proposed a lethal injection of potassium followed by a period of warm ischemia lasting between 45 in mice [11] and 60 min in pig [12], even reaching 150min which is closer to the timing of Class III DCD.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Modeling of DCD Class III Donation: Paving the Way for the Increased Use of This Challenging Donor Type

Soussi

Rod

Thuillier

et al. 2019

BioMed Research International

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Deceased after circulatory death (DCD) donors offer a viable solution to the current organ shortage, particularly the Maastricht Class III (arrest subsequent to cessation of life support in the hospital). Although current results from these donors are very satisfactory, the number of included donors is too low and future expansion of inclusion criteria will likely decrease organ quality, with negative consequences on the complication rate. This donor type thus represents a priority in terms of scientific exploration, so as to study it in controlled settings and prepare for future challenges. Hence, we mimicked the DCD Class III clinical conditions a Large White pig model. Herein, we detail the different strategies attempted to attain our objectives, including technical approaches such as animal positioning and ventilator settings, as well as pharmacological intervention to modulate blood pressure and heart rate. We highlight the best combination of factors to successfully reproduce DCD Class III conditions, with perfusion pressures and functional warm ischemia (hypoperfusion) closely resembling clinical situations. Finally, we detail the functional and histological impacts of these conditions. Such a model could be of critical value to explore novel management alternative for these donors, presenting a uniquely adapted platform for such therapeutics as normothermic regional circulation and/or pharmacological intervention.

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“…H 2 S is an endogenously produced gaseous signaling molecule and is maintained at physiologic concentrations in mammalian systems . Sodium sulfide, a H 2 S donor, has been used in the study of cytoprotective effects of H 2 S . Nevertheless, the role of H 2 S in cerebral ischemia remains controversial .…”

Section: Discussionmentioning

confidence: 99%

Sodium Sulfide, a Hydrogen Sulfide‐Releasing Molecule, Attenuates Acute Cerebral Ischemia in Rats

et al. 2016

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The effect of a hydrogen sulfide releasing molecule (Na2S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model

Cited by 15 publications

References 36 publications

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

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

Preclinical Modeling of DCD Class III Donation: Paving the Way for the Increased Use of This Challenging Donor Type

Sodium Sulfide, a Hydrogen Sulfide‐Releasing Molecule, Attenuates Acute Cerebral Ischemia in Rats

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The effect of a hydrogen sulfide releasing molecule (Na2S) on the cold storage of livers from cardiac dead donor rats. A study in an ex vivo model

Cited by 15 publications

References 36 publications

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

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

Preclinical Modeling of DCD Class III Donation: Paving the Way for the Increased Use of This Challenging Donor Type

Sodium Sulfide, a Hydrogen Sulfide‐Releasing Molecule, Attenuates Acute Cerebral Ischemia in Rats

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Product

Resources

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

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