Effects of sodium thiosulfate during resuscitation from trauma-and-hemorrhage in cystathionine-γ-lyase knockout mice with diabetes type 1
Creators: name: Gröger, Michael
name: Hogg, Melanie
name: Abdelsalam, Essam
name: Kress, Sandra
name: Hoffmann, Andrea
name: Stahl, Bettina
name: Calzia, Enrico
name: Wachter, Ulrich
name: Vogt, Josef A.
name: Wang, Rui
name: Merz, Tamara
name: Radermacher, Peter
name: McCook, Oscar
Publisher: name: Universität Ulm
Year: 2022
Subjects: subject: ureagenesis
subject: cystathionine-β-synthase
subject: IκBα
subject: glucocorticoid receptor
subject: DDC 610 / Medicine &amp; health
subject: Gluconeogenesis
subject: Hydrogen sulfide
subject: Receptors, Glucocorticoid
subject: Lipolysis
subject: Heme oxygenase-1
subject: Gluconeogenese
subject: Glucocorticosteroidrezeptor
subject: Lipolyse
subject: Schwefelwasserstoff

description: Background Sodium thiosulfate (STS) is a recognized drug with antioxidant and H2S releasing properties. We recently showed that STS attenuated organ dysfunction and injury during resuscitation from trauma-and-hemorrhage in CSE-ko mice, confirming its previously described organ-protective and anti-inflammatory properties. The role of H2S in diabetes mellitus type 1 (DMT1) is controversial: genetic DMT1 impairs H2S biosynthesis, which has been referred to contribute to endothelial dysfunction and cardiomyopathy. In contrast, development and severity of hyperglycemia in streptozotocin(STZ)-induced DMT1 was attenuated in CSE-ko mice. Therefore, we tested the hypothesis whether STS would also exert organ-protective effects in CSE-ko mice with STZ-induced DMT1, similar to our findings in animals without underlying co-morbidity. Methods Under short-term anesthesia with sevoflurane and analgesia with buprenorphine CSE-ko mice underwent DMT1-induction by single STZ injection (100 μg⋅g–1). Seven days later, animals underwent blast wave-induced blunt chest trauma and surgical instrumentation followed by 1 h of hemorrhagic shock (MAP 35 ± 5 mmHg). Resuscitation comprised re-transfusion of shed blood, lung-protective mechanical ventilation, fluid resuscitation and continuous i.v. norepinephrine together with either i.v. STS (0.45 mg⋅g–1) or vehicle (n = 9 in each group). Lung mechanics, hemodynamics, gas exchange, acid–base status, stable isotope-based metabolism, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, chemokines, and immunoblotting. Results Diabetes mellitus type 1 was associated with more severe circulatory shock when compared to our previous study using the same experimental design in CSE-ko mice without co-morbidity. STS did not exert any beneficial therapeutic effect. Most of the parameters measured of the inflammatory response nor the tissue expression of marker proteins of the stress response were affected either. Conclusion In contrast to our previous findings in CSE-ko mice without underlying co-morbidity, STS did not exert any beneficial therapeutic effect in mice with STZ-induced DMT1, possibly due to DMT1-related more severe circulatory shock. This result highlights the translational importance of both integrating standard ICU procedures and investigating underlying co-morbidity in animal models of shock research.