Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts

Srinivasan, Pramod Kadaba; Fet, Ngwi; Berne, Christian; Afify, Mohamed; Doorschodt, Benedict M.; Yagi, Shintaro; Echten‐Deckert, Gerhild van; Tolba, René

doi:10.12659/aot.889958

Cited by 8 publications

(3 citation statements)

References 57 publications

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“…DCD grafts are subjected to WI; transplantation of such organ grafts leads to inferior posttransplant outcome and eventually organ failure [7,9]. However, improved preservation techniques have improved DCD graft posttransplant performance [12,30,31]. In our previous study, we demonstrated the beneficial effects of VSOP+NO liver persufflation for 24 h [12].…”

Section: Discussionmentioning

confidence: 99%

“…WI followed by reperfusion has deleterious effects on the graft, which is known to cause PNF or PDF [12,31,32]. Research has shown that increased PVP levels were the direct cause for PDF due to impaired sinusoidal endothelial cells [33,34].…”

Section: Discussionmentioning

confidence: 99%

“…Bile is synthesized via an energy-dependent process in liver cells; this process is highly sensitive to episodes of WI and cold ischemia [31,44]. Bile production is a major functional parameter of liver function.…”

Section: Discussionmentioning

confidence: 99%

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Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts

Porschen

Srinivasan²,

Iwasaki³

et al. 2016

Eur Surg Res

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Background/Aim: Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. Materials and Methods: Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4°C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. Results: Data are presented as mean ± SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 ± 5.3, 63.2 ± 17.3, 25.6 ± 3.9, and 82.8 ± 27.3 U/l) and lactate dehydrogenase levels (289.4 ± 41.2, 2,139.4 ± 542.7, 577.2 ± 117.2, and 2,429 ± 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 ± 0.3, 2.7 ± 1, 1.0 ± 0, and 3.9 ± 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 ± 1, 21.2 ± 3.1, 16.1 ± 1, and 23.2 ± 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 ± 0.17, 1.8 ± 0.2, 2.7 ± 0.2, and 2.6 ± 0.1 μmol/l). Bile production levels showed no statistical significance (23.2 ± 3.8, 27.3 ± 1.8, 43.5 ± 18, and 31 ± 2.5 μl/45 min). Conclusion: Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts

Porschen

Srinivasan²,

Iwasaki³

et al. 2016

Eur Surg Res

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Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare

et al. 2016

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Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer's, Parkinson's and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer's Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed.

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Bioactivity profiling of the extremolyte ectoine as a promising protectant and its heterologous production

Zhu

et al. 2022

3 Biotech

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Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts

Abstract: Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.

Cited by 8 publications

References 57 publications

Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts

Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts

Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare

Bioactivity profiling of the extremolyte ectoine as a promising protectant and its heterologous production

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