The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study

Pagano, Domenico; Oliva, Elisabetta; Khouzam, Simone; Tuzzolino, Fabio; Cintorino, Davide; Petri, Sergio Li; Francesco, Fabrizio di; Ricotta, Calogero; Bonsignore, Pasquale; Tropea, Alessandro; Calamia, Sergio; Costanzo, Federico; Luca, Angelo; Gruttadauria, Salvatore

doi:10.1186/s12893-018-0455-7

Cited by 8 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver IRI is a complex pathophysiological process involving multiple factors and is an important cause of poor prognosis and multiple organ failure in patients with complex liver surgery and liver transplantation (Pagano et al, 2018). Our current research showed that liver ischemia for 1 h followed by reperfusion for 6 h led to a significant increase in ALT and AST levels.…”

Section: Discussionmentioning

confidence: 54%

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

et al. 2020

View full text Add to dashboard Cite

Liver ischemia-reperfusion injury (IRI) is a common clinical event with high morbidity in patients undergoing complex liver surgery or having abdominal trauma. Inflammatory and oxidative stress responses are the main contributing factors in liver IRI. The iridoid glucoside aucubin (AU) has good anti-inflammatory and antioxidative effects; however, there are no relevant reports on the protective effect of glucosides on hepatic IRI. The purpose of this study was to determine whether AU pretreatment could prevent liver IRI and to explore the mechanism. Sprague-Dawley rats were randomly divided into five groups. The sham operation and IRI control groups were given intraperitoneal injections of normal saline, while the AU low-dose (AU-L) group, AU medium-dose (AU-M) group, and AU high-dose (AU-H) group were given intraperitoneal injections of AU at doses of 1, 5, and 10 mg/kg/day, respectively. After 10 d, liver IRI (70% liver ischemia for 1 h, reperfusion for 6 h) was surgically established in all groups except the sham group. Our results confirmed that liver injury was significantly aggravated after hepatic ischemia-reperfusion. AU alleviated the increase of transaminase and pathological changes induced by ischemia-reperfusion and improved liver damage. AU could also ameliorate the inflammatory and oxidative stress responses induced by ischemia-reperfusion and reduced expression of high mobility group protein (HMG)B1, receptor for advanced glycation end-products (RAGE), tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and reactive oxygen species (ROS). Moreover, AU reduced ischemia-reperfusion-induced mitochondrial dysfunction and cells apoptosis, increased peroxisome proliferatoractivated receptor g coactivator (PGC)-1a and uncoupling (UCP)2 protein expression, and reduced caspase-3, cleaved caspase-3, and Cytochrome P450 proteins (CYP) expression. To determine expression levels of the Toll-like receptor (TLR)-4/ nuclear factor-kB (NF-kB) pathway-related proteins in vitro and in vivo, we also measured TLR-4, myeloid differentiation factor88 (MyD88), NF-kB P65, p-P65, Ikappa-B-alpha (IkB-a), and p-IkB-a levels. The results showed that AU effectively

show abstract

Section: Discussionmentioning

confidence: 54%

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Liver IRI is a complex pathophysiological process involving multiple factors that is associated with a cause of poor prognosis and multiple organ failure in patients after liver transplantation (14). Previous studies demonstrated that the liver IR is characterized by oxidative-stress responses and release of ROS that directly lead to tissue damage and initiates a cascade of deleterious cellular responses leading to in ammation, cell death, and ultimate organ failure (15,16).…”

Section: Discussionmentioning

confidence: 99%

Effects of fullerenol C60 on liver tissue in liver ischemia reperfusion injury in rats undergoing sevoflurane anesthesia Subtitle: Fullerenol C60 in liver ischemia reperfusion injury in rats

Yavuz

Tuna

Ozdemir

et al. 2023

Preprint

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of fullerenol C60 on rat liver tissue in liver ischemia reperfusion injury (IRI) model undergoing sevoflurane anesthesia to evaluate the ability of nanoparticles to prevent hepatic complications. A total of 36 adult female Wistar Albino rats were divided into six groups each containing six as follows: sham group (Group S), the fullerenol C60 group (Group FC60), the ischemia-reperfusion group (Group IR), and the ischemia-reperfusion-sevoflurane group (Group IR-Sevo), ischemia-reperfusion-fullerenol C60 group (Group IR-FC60), ischemia-reperfusion-fullerenol C60-sevoflurane group (Group IR-FC60-Sevo). Fullerenol C60 100 mg/kg was administrated in Group IR-FC60 and IR-FC60-Sevo. In IR groups 2 hours of ischemia and 2 hours of reperfusion were performed. At the end of the reperfusion, liver tissues were removed for biochemical assays, and histopathological examinations. Hepatocyte degeneration, sinüsoidal dilatation, prenecrotic cell, MN celluler infiltration in the parenchyma were significantly higher in Group IR than all other groups. TBARS level was significantly higher in Group IR than other groups and the lowest TBARS level was in Group IR-FC60 than other groups except Group S and FC60. CAT and GST activities reduced in Groups IR than all other groups. Fullerenol C60 has protective effects against liver IR injury in rats under sevoflurane anesthesia. The use of fullerenol C60 could reduce the adverse effects of IRI and associated costs in liver transplantation surgery.

show abstract

“…NAC could be a complementary tool when used in addition to other approaches that are under investigation. 51,52…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial

Gómez‐Gavara

Moya-Herráiz²,

Hervás

et al. 2021

Transplantation

View full text Add to dashboard Cite

Original Clinical Science-Liver Background. N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. Objective. To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. Methods. Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). Results. The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). Conclusions. N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.

show abstract

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study

Cited by 8 publications

References 19 publications

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

Aucubin Attenuates Liver Ischemia-Reperfusion Injury by Inhibiting the HMGB1/TLR-4/NF-κB Signaling Pathway, Oxidative Stress, and Apoptosis

Effects of fullerenol C60 on liver tissue in liver ischemia reperfusion injury in rats undergoing sevoflurane anesthesia Subtitle: Fullerenol C60 in liver ischemia reperfusion injury in rats

The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial

Contact Info

Product

Resources

About