Browsing by Author "Zhang, M.Y."
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Evaluating the Effects of Subnormothermic Perfusion with AP39 in a Novel Blood-Free Model of Ex Vivo Kidney Preservation and Reperfusion(International journal for molecular sciences, 2021) Juriasingani, S.; Jackson, A.; Zhang, M.Y.; Ruthirakanthan, A.; Dugbartey, G.J.; Sogutdelen, E.; Levine, M.; Mandurah, M.; Whiteman, M.; Luke, P.; Sener, A.The use of blood for normothermic and subnormothermic kidney preservation hinders the translation of these approaches and promising therapeutics. This study evaluates whether adding hydrogen sulfide donor AP39 to Hemopure, a blood substitute, during subnormothermic perfusion improves kidney outcomes. After 30 min of renal pedicle clamping, porcine kidneys were treated to 4 h of static cold storage (SCS-4 ◦C) or subnormothermic perfusion at 21 ◦C with Hemopure (H-21 ◦C), Hemopure + 200 nM AP39 (H200nM-21 ◦C) or Hemopure + 1 µM AP39 (H1µM-21 ◦C). Then, kidneys were reperfused with Hemopure at 37 ◦C for 4 h with metabolic support. Perfusate composition, tissue oxygenation, urinalysis and histopathology were analyzed. During preservation, the H200nM-21 ◦C group exhibited significantly higher urine output than the other groups and significantly higher tissue oxygenation than the H1µM-21 ◦C group at 1 h and 2h. During reperfusion, the H200nM-21 ◦C group exhibited significantly higher urine output and lower urine protein than the other groups. Additionally, the H200nM-21 ◦C group exhibited higher perfusate pO2 levels than the other groups and significantly lower apoptotic injury than the H-21 ◦C and the H1µM-21 ◦C groups. Thus, subnormothermic perfusion at 21 ◦C with Hemopure + 200 nM AP39 improves renal outcomes. Additionally, our novel blood-free model of ex vivo kidney preservation and reperfusion could be useful for studying other therapeutics.Item H2S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation(Pharmacological Research, 2021) Dugbartey, G.J.; Juriasingani, S.; Zhang, M.Y.; Sener, A.Cold ischemia-reperfusion injury (IRI) is an inevitable and unresolved problem that poses a great challenge in solid organ transplantation (SOT). It represents a major factor that increases acute tubular necrosis, decreases graft survival, and delays graft function. This complicates graft quality, post-transplant patient care and organ transplantation outcomes, and therefore undermines the success of SOT. Herein, we review recent advances in research regarding novel pharmacological strategies involving the use of different donor molecules of hydrogen sulfide (H2S), the third established member of the gasotransmitter family, against cold IRI in different experimental models of SOT (kidney, heart, lung, liver, pancreas and intestine). Additionally, we discuss the molecular mechanisms underlying the effects of these H2S donor molecules in SOT, and suggestions for clinical translation. Our reviewed findings showed that storage of donor organs in H2S-supplemented preservation solution or administration of H2S to organ donor prior to organ procurement and to recipient at the start and during reperfusion is a novel, simple and cost-effective pharmacological approach to minimize cold IRI, limit posttransplant complications and improve transplantation outcomes. In conclusion, experimental evidence demonstrate that H2S donors can significantly mitigate cold IRI during SOT through inhibition of a complex cascade of interconnected cellular and molecular events involving microcirculatory disturbance and microvascular dysfunction, mitochondrial injury, inflammatory responses, cell damage and cell death, and other damaging molecular pathways while promoting protective pathways. Translating these promising findings from bench to bedside will lay the foundation for the use of H2S donor molecules in clinical SOT in the future.