Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation

Zhang, Bo; Liu, Qiu‐Hua; Zhou, Cuijie; Hu, Ming-zheng; Qian, Haixin

doi:10.3892/etm.2016.3762

Cited by 20 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In hypoxic–ischemic conditions, as occurs also in organs during cold storage, eNOS promotes vasodilation increasing blood flow, and this event is responsible for increasing graft preservation [ 19 ]. Recently, Zhang et al reported that eNOS-derived NO production significantly attenuates hepatic I/R injury, suggesting that NOS overexpression may constitute a promising therapeutic approach to prevent liver I/R injury following liver transplantation [ 20 ]. Russo et al documented that the addition of simvastatin to the storage solution increased eNOS content, prevented liver damage, and improved endothelial dysfunction [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

Pasqua

Berardo

Cagna

et al. 2021

IJMS

View full text Add to dashboard Cite

We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

Pasqua

Berardo

Cagna

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In particular, a NO releasing hydrogel has been documented to enhance the therapeutic effects of mesenchymal stem cell therapy for hind limb ischemia [ 89 ]. In this context, overexpression of eNOS was reported to be protective against ischemia/reperfusion injury [ 90 ]. The eNOS-derived NO was proven to be essential for both early and late vascular recovery in response to hind limb ischemia [ 91 ].…”

Section: Resultsmentioning

confidence: 99%

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

et al. 2021

View full text Add to dashboard Cite

Plicosepalus acacia (Fam. Loranthaceae) has been reported to possess hypoglycemic, antioxidant, antimicrobial, and anti-inflammatory effects. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of a high content of polyphenolic compounds that are attributed to the therapeutic effects of the crude extract. In addition, methyl gallate and quercetin were detected as major phytomedicinal agents at concentrations of 1.7% and 0.062 g%, respectively, using high-performance thin layer chromatography (HPTLC). The present study investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on hind limb ischemia induced in type 1 diabetic rats. Histopathological examination revealed that treatment with P. acacia extract, methyl gallate, and quercetin decreased degenerative changes and inflammation in the ischemic muscle. Further biochemical assessment of the hind limb tissue showed decreased oxidative stress, increased levels of nitric oxide and endothelial nitric oxide synthase (eNOS), and enhancement of the levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in the groups treated with methyl gallate and quercetin. Expression levels of hypoxia inducible factor-1 alpha (HIF-1α), VEGF, fibroblast growth factor-2 (FGF-2), and miR-146a were upregulated in the muscle tissue of methyl gallate- and quercetin-treated groups along with downregulation of nuclear factor kappa B (NF-κB). In conclusion, P. acacia extract and its isolated compounds, methyl gallate and quercetin, mediated therapeutic angiogenesis in diabetic hind limb ischemia.

show abstract

“…Some studies have demonstrated the hepatoprotective effect of genetic eNOS overexpression in small-for-size liver transplantation and illustrated the importance of promoting eNOS expression for hepatoprotection[ 61 ]. However, there is insufficient evidence for a protective effect of eNOS overexpression, and evidence that eNOS overexpression is detrimental to HIRI[ 62 ].…”

Section: Regulating Inos and Enos Expression To Protect Hirimentioning

confidence: 99%

New progress in understanding roles of nitric oxide during hepatic ischemia-reperfusion injury

Zhang¹,

Liu²,

Yang³

et al. 2022

WJH

View full text Add to dashboard Cite

Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.

show abstract

Protective effect of eNOS overexpression against ischemia/reperfusion injury in small-for-size liver transplantation

Cited by 20 publications

References 35 publications

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

New progress in understanding roles of nitric oxide during hepatic ischemia-reperfusion injury

Contact Info

Product

Resources

About