L-Alanyl-Glutamine Attenuates Oxidative Stress in Liver Transplantation Patients

Barros, Marcos Aurélio Pessoa; Vasconcelos, Paulo Roberto Leitão de; Souza, Carolina Augusto de; Andrade, Geanne Matos de; Moraes, M. O.; Costa, Paulo; Coelho, Gustavo; Garcia, José Huygens Parente

doi:10.1016/j.transproceed.2015.08.001

Cited by 17 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a meta analysis of several clinical studies on NAC treatment the authors concluded that NAC administration improved transaminase levels but without patient or graft survival correlation [84]. L-Alanyl-Glutamine has promising results decreasing lipid peroxidation after liver transplantation [85] but more clinical results are required. Another antioxidant tested for IRI is melatonin, an antioxidant produced in the pineal gland that showed a protective effect against IRI, supraphysiological doses of melatonin improve the general outcome after liver resection [86], [87].…”

Section: Translation Into the Clinical Settingmentioning

confidence: 99%

ROS homeostasis, a key determinant in liver ischemic-preconditioning

Prieto

Monsalve

2017

Redox Biology

View full text Add to dashboard Cite

Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury but also required for the induction of the stress response that limits tissue injury and underlies the protection provided by ischemic-preconditioning protocols. Liver steatosis is an important risk factor for liver transplant failure. Liver steatosis is associated with mitochondrial dysfunction and excessive mitochondrial ROS production. Studies aiming at decreasing the sensibility of the steatotic liver to ischemia-reperfusion injury using pre-conditioning protocols, have shown that the steatotic liver has a reduced capacity to respond to these protocols. Recent studies indicate that these effects are related to a reduced capacity of the steatotic liver to respond to elevated ROS levels following reperfusion by inducing a compensatory response. This failure to respond to ROS is associated with reduced levels of antioxidants, mitochondrial damage, hepatocyte cell death, activation of the immune system and induction of pro-fibrotic mediators.

show abstract

Section: Translation Into the Clinical Settingmentioning

confidence: 99%

ROS homeostasis, a key determinant in liver ischemic-preconditioning

Prieto

Monsalve

2017

Redox Biology

View full text Add to dashboard Cite

show abstract

“…We also appraised the activity of glutathione peroxidase (GPx) and the rate of glutathione (GSH) following Flohe and Gunzler reaction by measuring the reduction of the absorbance of GSH at 412 nm in presence of H 2 O 2 [29,30]. GSH was expressed as µg/mg of protein and GPx activity was expressed as µmol GSH/min/mg of protein.…”

Section: Animals and Methodsmentioning

confidence: 99%

Nitrite enhances liver graft protection against cold ischemia reperfusion injury through a NOS independent pathway

Cherif-Sayadi

Ayed-Tka

Zaoualí

et al. 2017

Libyan Journal of Medicine

View full text Add to dashboard Cite

Introduction: Nitrite has been found to protect liver graft from cold preservation injury. However, the cell signaling pathway involved in this protection remains unclear. Here, we attempt to clarify if the NOS pathway by using the NOS inhibitor, L-NAME (L-NG-Nitroarginine methyl ester). Animals and methods: Rat livers were conserved for 24 h at 4°C in (IGL-1) solution enriched or not with nitrite at 50 nM. In a third group, rats were pretreated with 50 mg/kg of L-NAME before their liver procurement and preservation in IGL-1 supplemented with nitrite (50 nM) and L-NAME (1 mM). After 24 h of cold storage, rat livers were ex-vivo perfused at 37°C during 2 h. Control livers were perfused without cold storage. Results: Nitrite effectively protected the rat liver grafts from the onset of cold I/R injury. L-NAME treatment did not abolish the beneficial effects of nitrite. Liver damage, protein oxidation and lipid peroxidation remained at low levels in both nitrite-treated groups when compared to IGL-1 group. Antioxidant enzyme activities and functional parameters were unchanged after NOS inhibition. Conclusion: Despite NOS inhibition by L-NAME, nitrite can still provide hepatic protection during cold I/R preservation. This suggests that nitrite acts through a NOS-independent pathway.

show abstract

“…The antioxidative treatment approach with the aim of scavenging ROS, which increase during brain death and IRI, was also addressed in the clinical setting; however, they could not show an improvement of survival in LT and kidney transplantation [55,56,57,58], though short-term liver function was shown to be improved by the application of ascorbic acid and donor ventilation with sevoflurane. Sevoflurane was also reported by Minou et al [58] to be protective in steatotic livers.…”

Section: Approaches For Preconditioning Organs In Order To Improve Trmentioning

confidence: 99%

Control of Ischemia-Reperfusion Injury in Liver Transplantation: Potentials for Increasing the Donor Pool

Kahn

Schemmer

2018

Visc Med

View full text Add to dashboard Cite

Background: Organ shortage is a growing problem, with a rising number of organs being harvested from extended criteria donors, and this trend will further continue to increase as organ donors are getting older and have more comorbidities. Since this fact is immutable, efforts have been made to reduce the extent of ischemia-reperfusion injury (IRI) as well as of direct and indirect harvest-related graft injury which affects all organs in a more or less distinct way. Methods: In liver transplantation (LT), the activation of Kupffer cells during organ reperfusion, thus provoking microcirculatory disturbances, hypoxia, and endothelial cell injury, is one of the key mechanisms causing graft dysfunction. Multiple approaches have been taken in order to find efficient preconditioning methods by pharmacological pretreatment, controlled induction of ischemia, controlled denervation of donor organs, and reconditioning with machine perfusion to prevent IRI, whereas marginal organs (i.e. steatotic grafts) are especially vulnerable. Results: The above-mentioned approaches have been pursued in experimental and clinical settings. At this time point, however, there is not yet enough clinical evidence available to recommend any particular drug pretreatment or any other intervention for organ preconditioning prior to transplantation. Conclusion: The multifactorial pathophysiology in the setting of IRI in LT requires a multimodal therapeutic approach with the integration of pharmacological and technical means being applied to the donor, the organ per se, and the recipient. Currently, there is no consensus on standardized pretreatment of donor organs in order to improve the transplant outcome.

show abstract

L-Alanyl-Glutamine Attenuates Oxidative Stress in Liver Transplantation Patients

Cited by 17 publications

References 29 publications

ROS homeostasis, a key determinant in liver ischemic-preconditioning

ROS homeostasis, a key determinant in liver ischemic-preconditioning

Nitrite enhances liver graft protection against cold ischemia reperfusion injury through a NOS independent pathway

Control of Ischemia-Reperfusion Injury in Liver Transplantation: Potentials for Increasing the Donor Pool

Contact Info

Product

Resources

About