Dexmedetomidine attenuates hepatic ischemia-reperfusion injury-induced apoptosis via reducing oxidative stress and endoplasmic reticulum stress

Zhang, Shixia; Tang, Jilang; Sun, Cheng; Zhang, Nuannuan; Ning, Xiaqing; Wang, Jiaqi

doi:10.1016/j.intimp.2023.109959

Cited by 11 publications

(3 citation statements)

References 42 publications

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“…The dimerization complex binds to DNA at specific sites of AP-1 in the promoter and enhancer regions of target genes, thereby translating extracellular signals into changes in gene expression, such as activation of the NF-κB pathway, which is involved in the regulation of inflammatory activation and cell survival-related processes 38 . Several studies have shown that in HIRI, the MAPK-extracellular signal-regulated kinase (ERK) signaling pathway is usually in an abnormally high state of activity, with multiple cytokines activating ERK1 and ERK2 39 , 40 , and that activated ERK phosphorylates the c-Fos transcription factor, which in turn plays a direct role in inflammatory regulation 41 . Similarly, FOS was identified as a potential risk factor for aging livers to be more susceptible to HIRI in human liver transplantation sequencing profiles, suggesting an important role of FOS involved in the pro-inflammatory effects of HIRI 42 .…”

Section: Discussionmentioning

confidence: 99%

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Tan,

Lu,

Chen

et al. 2024

Sci Rep

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Hepatic ischemia–reperfusion injury (HIRI) elicits an immune-inflammatory response that may result in hepatocyte necrosis and apoptosis, ultimately culminating in postoperative hepatic dysfunction and hepatic failure. The precise mechanisms governing the pathophysiology of HIRI remain incompletely understood, necessitating further investigation into key molecules and pathways implicated in disease progression to guide drug discovery and potential therapeutic interventions. Gene microarray data was downloaded from the GEO expression profile database. Integrated bioinformatic analyses were performed to identify HIRI signature genes, which were subsequently validated for expression levels and diagnostic efficacy. Finally, the gene expression was verified in an experimental HIRI model and the effect of anti-IL17A antibody intervention in three time points (including pre-ischemic, post-ischemic, and at 1 h of reperfusion) on HIRI and the expression of these genes was investigated. Bioinformatic analyses of the screened characterized genes revealed that inflammation, immune response, and cell death modulation were significantly associated with HIRI pathophysiology. CCL2, BTG2, GADD45A, FOS, CXCL10, TNFRSF12A, and IL-17 pathway were identified as key components involved in the HIRI. Serum and liver IL-17A expression were significantly upregulated during the initial phase of HIRI. Pretreatment with anti-IL-17A antibody effectively alleviated the damage of liver tissue, suppressed inflammatory factors, and serum transaminase levels, and downregulated the mRNA expression of CCL2, GADD45A, FOS, CXCL10, and TNFRSF12A. Injection of anti-IL17A antibody after ischemia and at 1 h of reperfusion failed to demonstrate anti-inflammatory and attenuating HIRI benefits relative to earlier intervention. Our study reveals that the IL-17 pathway and related genes may be involved in the proinflammatory mechanism of HIRI, which may provide a new perspective and theoretical basis for the prevention and treatment of HIRI.

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Section: Discussionmentioning

confidence: 99%

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Tan,

Lu,

Chen

et al. 2024

Sci Rep

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“…On the other hand, this result is consistent with the finding that DEX reduces moderate-to-extreme hepatic IRI, which is the inducing factor of graft dysfunction. DEX has been shown to reduce hepatic IRI through multiple pathways, including decreasing oxidative stress, endoplasmic reticulum stress, and apoptotic pathways ( Zhang et al, 2023 ). Notably, the total sample size of the current study may not be sufficient to reveal the role of DEX in postoperative liver function.…”

Section: Discussionmentioning

confidence: 99%

Effect of dexmedetomidine on liver transplantation: a meta-analysis

Jia

Guo

et al. 2023

Front. Pharmacol.

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Background: Dexmedetomidine (DEX), an adjuvant anesthetic, may improve the clinical outcomes of liver transplantation (LT).Methods: We summarized the relevant clinical trials of DEX in patients undergoing LT. As of 30 January 2023, we searched The Cochrane Library, MEDLINE, EMBASE, Clinical Trial.gov and the WHO ICTRP. The main outcomes were postoperative liver and renal function. The random effect model or fixed effect model was used to summarize the outcomes across centers based on the differences in heterogeneity.Results: The meta-analysis included nine studies in total. Compared with the control group, the DEX group had a reduced warm ischemia time (MD-4.39; 95% CI-6.74−2.05), improved postoperative liver (peak aspartate transferase: MD-75.77, 95% CI-112.81−38.73; peak alanine transferase: MD-133.51, 95% CI-235.57−31.45) and renal function (peak creatinine: MD-8.35, 95% CI-14.89−1.80), and a reduced risk of moderate-to-extreme liver ischemia-reperfusion injury (OR 0.28, 95% CI 0.14-0.60). Finally, the hospital stay of these patients was decreased (MD-2.28, 95% CI-4.00−0.56). Subgroup analysis of prospective studies showed that DEX may have better efficacy in living donors and adult recipients.Conclusion: DEX can improve short-term clinical outcomes and shorten the hospital stay of patients. However, the long-term efficacy of DEX and its interfering factors deserves further study.Systematic Review: identifier CRD42022351664.

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“…Dexmedetomidine, a highly specific α2-adrenergic agonist, is often employed to induce sedation and relieve pain during the anesthetic process. Studies have demonstrated that dexmedetomidine can mitigate ischemia-reperfusion injury by reducing oxidative stress (9). Recent clinical investigations have also suggested dexmedetomidine's potential protective role in reducing AKI incidence (10,11).…”

Section: Introductionmentioning

confidence: 99%

The effectiveness of dexmedetomidine for preventing acute kidney injury after surgery: a systematic review and meta-analysis

Zhao,

Tang,

Shen

et al. 2024

Front. Med.

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BackgroundPostoperative acute kidney injury (AKI) is a serious and distressing complication connected to various adverse outcomes following the surgical operation. Controversy remains regarding the dexmedetomidine’s preventive impact on postoperative AKI. Therefore, this investigation aims to explore the efficiency and safety of dexmedetomidine in preventing AKI after surgical operation.MethodsWe systematically searched electronic databases such as PubMed, Embase, Web of Science, and the Cochrane Library to detect eligible randomized controlled studies that used dexmedetomidine for the prevention of AKI following operation up to April 30, 2023. The main outcome evaluated was AKI incidence. The evidence quality was assessed employing the Grading of Recommendations Assessment, Development, and Evaluation.ResultsThe meta-analysis included 25 trials, including 3,997 individuals. Of these, 2,028 were in the dexmedetomidine group, and 1,969 were in the control group. The result showed that patients administered dexmedetomidine significantly decreased the AKI incidence following surgical operation in contrast to the control group (risk ratio, 0.60; 95% confidence intervals, 0.45–0.78; p < 0.05; I2 = 46%). In addition, dexmedetomidine decreased the period of hospitalization in both the intensive care unit (ICU) and the hospital while also reducing postoperative delirium (POD) occurrence. However, dexmedetomidine elevated the incidence of bradycardia but did not have a significant impact on other indicators.ConclusionOur meta-analysis indicates that the dexmedetomidine treatment reduces the postoperative AKI and POD risk while also shortening the time of hospitalization in the ICU and hospital. However, it is connected to an increased bradycardia risk.

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Dexmedetomidine attenuates hepatic ischemia-reperfusion injury-induced apoptosis via reducing oxidative stress and endoplasmic reticulum stress

Cited by 11 publications

References 42 publications

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Effect of dexmedetomidine on liver transplantation: a meta-analysis

The effectiveness of dexmedetomidine for preventing acute kidney injury after surgery: a systematic review and meta-analysis

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