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

Zhang, Yiping; Liu, Xin-Ran; Yang, Mei-wen; Yang, Shu‐Long; Hong, Fashui

doi:10.4254/wjh.v14.i3.504

Cited by 11 publications

(7 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NO produced by the constitutive form of NO synthase (eNOS) has a protective effect by improving hepatic microcirculation and counteracting the offensive properties of ROS. In contrast, an increased level of NO released following activation of the inducible form of NOS (iNOS) during reperfusion contributes to peroxynitrite formation, leading to lipoperoxidation, endothelial dysfunction, aggravation of proin ammatory response and worsening of the liver injury [39]. Interestingly, our results revealed that TQloaded SNEDDS suppressed iNOS expression, suggesting that TQ-loaded SNEDDS has maintained a physiological amount of NO.…”

Section: Discussionmentioning

confidence: 61%

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury

Bahloul

Chaabani

Zahra

et al. 2023

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

In the present study, a self nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the e ciency of TQ in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ loaded SNEDDS. Biochemical analyses, haematoxylin-eosin staining, indirect immuno uorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, in ammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration and iNOS protein expression. In addition, this formulation exerted an anti-in ammatory effect evidenced by reduced plasma CRP concentration, MPO activity, gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS signi cantly protects rat liver from I/R injury.

show abstract

Section: Discussionmentioning

confidence: 61%

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury

Bahloul

Chaabani

Zahra

et al. 2023

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

show abstract

“…It is well documented that ATP7B is intertwined with lipid metabolism and can damage crucial cellular organelles for ROS energy metabolism during the development of Wilson’s disease ( 31 , 32 ). Excess ROS production can inhibit other antioxidant defense mechanisms in HIRI, leading to increased oxidative damage ( 33 , 34 ). Thus, further exploration of the role of ATP7B in the pathogenesis of HIRI is necessary for future detailed insights.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning

Xiao,

Huang,

Yuan

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Background and aimsCuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI).MethodsThe datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes.ResultsSeventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues.ConclusionOur findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.

show abstract

“…There is evidence that NO deficiency occurs during ischemia-reperfusion [ 30 ]. It is assumed that early endothelial damage worsens the production of NO, which eliminates the endogenous antineutrophilic effects of NO [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass

Radovskiy,

Bautin,

Marichev

et al. 2023

Pathophysiology

View full text Add to dashboard Cite

Objective. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. Methods. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, n = 5). Animals in the control group (CPB-contr, n = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. Results. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, p < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, p < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, p < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; p = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; p = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; p = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. Conclusions. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.

show abstract

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

Cited by 11 publications

References 62 publications

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury

Thymoquinone-loaded self-nano-emulsifying drug delivery system against ischemia/reperfusion injury

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning

NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass

Contact Info

Product

Resources

About