Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways

Rabie, Mostafa A.; Zaki, Hala F.; Sayed, Helmy M.

doi:10.1016/j.bcp.2019.08.001

Cited by 18 publications

(18 citation statements)

References 59 publications

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“…PI3K/AKT signalling plays a vital role in hepatic I/R injury by suppressing pro‐apoptotic signals and inflammation 51 . Activating the PI3K/AKT signalling is conducive to the remission of hepatic I/R injury 51‐53 . Nrf2 activation facilitates cell protection in a PI3K‐dependent manner by reducing oxidative stress, hepatic inflammation and hepatocyte necrosis/apoptosis 54,55 .…”

Section: Discussionmentioning

confidence: 99%

“…51 Activating the PI3K/AKT signalling is conducive to the remission of hepatic I/R injury. [51][52][53] Nrf2 activation facilitates cell protection in a PI3K-dependent manner by reducing oxidative stress, hepatic inflammation and hepatocyte necrosis/apoptosis. 54,55 Nrf2 activation is a potent intervention that can protect hepatic I/R injury during and after surgery.…”

Section: Discussionmentioning

confidence: 99%

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Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Yan

Qiu

Zhang

et al. 2021

J Cellular Molecular Medi

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Hepatic ischaemia‐reperfusion (I/R) injury constitutes a tough difficulty in liver surgery. Dexmedetomidine (Dex) plays a protective role in I/R injury. This study investigated protective mechanism of Dex in hepatic I/R injury. The human hepatocyte line L02 received hypoxia/reoxygenation (H/R) treatment to stimulate cell model of hepatic I/R. The levels of pyroptosis proteins and inflammatory factors were detected. Functional rescue experiments were performed to confirm the effects of miR‐494 and JUND on hepatic I/R injury. The levels of JUND, PI3K/p‐PI3K, AKT/p‐AKT, Nrf2, and NLRP3 activation were detected. The rat model of hepatic I/R injury was established to confirm the effect of Dex in vivo. Dex reduced pyroptosis and inflammation in H/R cells. Dex increased miR‐494 expression, and miR‐494 targeted JUND. miR‐494 inhibition or JUND upregulation reversed the protective effect of Dex. Dex repressed NLRP3 inflammasome by activating the PI3K/AKT/Nrf2 pathway. In vivo experiments confirmed the protective effect of Dex on hepatic I/R injury. Overall, Dex repressed NLRP3 inflammasome and alleviated hepatic I/R injury via the miR‐494/JUND/PI3K/AKT/Nrf2 axis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Yan

Qiu

Zhang

et al. 2021

J Cellular Molecular Medi

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“…This signaling activates IKB kinase (IKK)-β, IKK-α, and the nuclear translocation of activated NF-κB [ 4 ]. Several studies have explored the role of HMGB1/TLR4 pathway intensification in hepatic ischemia-induced injury [ 35 , 36 , 37 ]. NLRPs are subfamilies of NOD-like receptors, members of the pattern recognition receptor family, which play a role in the recognition of ligands [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats

Mohamed

Younis

2022

Life

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Background: D-carvone is a monoterpene that exists in the essential oils of several plant species. Hepatic ischemia-reperfusion (Hep I/R) takes place clinically during different scenarios of liver pathologies. The aim of the current investigation is to disclose the hepato-protective actions of carvone against Hep I/R-induced damage and to reveal the underlying mechanism. Material and methods: Rats were assigned into five groups: sham and carvone plus sham groups, in which rats were administered either saline or carvone orally for three weeks prior to the induction of Hep I/R. In the Hep I/R group, rats were administered saline orally prior to the Hep I/R induction operation. The carvone 25 plus Hep I/R and Carvone 50 plus Hep I/R groups were administered carvone (25 and 50 mg/kg, respectively) for three weeks, followed by the induction of Hep I/R. Results: Liver ischemic animals demonstrated impaired liver function, several histopathological variations, and reduced levels of antioxidant enzyme activities. Furthermore, the Hep I/R groups showed the elevated gene expression of high-mobility group box 1 (HMGB1), toll-like receptors 4 (TLR4), nuclear factor kappa B (NFκB), and LR family pyrin domain containing 3 (NLP3), with subsequent escalated adhesion molecule 1 (ICAM-1), neutrophil infiltration, and several inflammatory mediators, including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), as well as apoptotic markers. Pretreatment with D-carvone alleviated ischemia/reperfusion-induced impaired liver function, diminished the histopathological deviations, and augmented the antioxidant enzymes. In addition, D-carvone mitigated the gene expression of HMGB1, TLR4, NFκB, and NLP3, with a subsequent reduction in ICAM-1, neutrophils infiltration, inflammatory mediators, and apoptotic markers. Conclusion: Rats pretreated with D-carvone exhibited hepato-protective actions against Hep I/R-induced damage via the downregulation of HMGB1, TLR4, NFκB, NLP3, associated inflammatory mediators, and apoptotic markers.

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“…It has been proven that telluric acid has a hepatoprotective effect by elevating the expression of eNOS, which is accompanied with elevated expression of p-PI3K and p-Akt proteins. Besides, the activation of PI3K/Akt also inhibits NF-κB and activates nuclear erythroid-related factor-2, reducing pro-inflammation cytokine expression and inducing anti-oxidative effects[ 42 ]. Moreover, through the PI3K/Akt pathway, apelin preconditioning can increase the expression of eNOS and counteract the pathological effects of the angiotensin II/angiotensin II type 1 receptor system in HIRI[ 43 ].…”

Section: Role Of Enos In Hirimentioning

confidence: 99%

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

Zhang¹,

Liu²,

Yang³

et al. 2022

WJH

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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.

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Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways

Cited by 18 publications

References 59 publications

Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Dexmedetomidine alleviates hepatic ischaemia‐reperfusion injury via the PI3K/AKT/Nrf2‐NLRP3 pathway

Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats

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

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