Resveratrol preconditioning protects hepatocytes against hepatic ischemia reperfusion injury via Toll-like receptor 4/nuclear factor-κB signaling pathway in vitro and in vivo

He, Diao; Guo, Zhen; Pu, Jing; Zheng, Daofeng; Wei, Xufu; Li, Rui; Tang, Chengyong; Wu, Zhongjun

doi:10.1016/j.intimp.2016.03.032

Cited by 47 publications

(31 citation statements)

References 27 publications

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“…2). This result suggested that RSV had a protective effect on LPS-induced tissue injury, which was consistent with other reports233539.…”

Section: Discussionsupporting

confidence: 93%

“…Moreover, the result showed the IL-1β and NO in high and low doses of RSV-treated groups were significant differences with those in blank control group, while other pro-inflammatory mediators, including IL-1, IL-6, IL-8, IL-10, iNOS, COX-2 and PGE2 in all RSV-treated groups showed no significant differences. This result was coincident with previous results that there were no significant differences between normal group and RSV-treated groups (The group only administrated with RSV and the group supplemented with RSV after stimulation)39515253, suggesting that at normal state, whether administration with RSV showed no significant differences on the evaluation of anti-inflammatory activity. Furthermore, our results also showed that the contents of NO and PGE2 were almost corresponding with the production of iNOS and COX-2, respectively, which further substantiated the rationale that iNOS is one of the key enzymes generating NO and PGE 2 is produced by the inducible enzyme COX-2.…”

Section: Discussionsupporting

confidence: 92%

“…It has been reported that all of the toll-like receptors are the first-type transmembrane proteins including TLR4, which is a crucial factor in triggering the inflammatory response by recognizing the associated ligands7. Then, the TLR4-mediated signal pathway activates the related signaling pathways, such as NF-kB and MAPK, which could regulate the release of proinflammatory mediators and cytokines39. At resting-state, NF-kBp65 is combing with the inhibitory protein IκB which can make NF-kB retained in the cytoplasm in an inactive forms of dimers.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the low content of P-IĸBα in LPS group attributed to its rapid degradation after stimulation. Despite western blotting is widely used in many mechanism researches, most of them are implemented on the basis of total protein and hardly on the cytoplasm and nucleus proteins, respectivley123945. At present, the expressions of proteins in tissue’s cytoplasm and nucleus as well as phosphorylated proteins in tissue’s nucleus could be speculated, but the changes of phosphorylated proteins in tissue’s cytoplasm remains incomprehensive and controversial, which needs further study.…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Wang

et al. 2017

Sci Rep

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Resveratrol (RSV) is a natural compound exhibiting anti-inflammatory effect, but the anti-inflammatory mechanism has not been fully understood. This study is aimed to evaluate the anti-inflammatory activity and mechanism of RSV in lipopolysaccharides-induced rats’ model. The visceral wet/dry weight ratios and the changes of hematologic and biochemical indices indicated that LPS- stimulation mainly caused damages to liver and lung, while pretreatment with RSV could alleviate the lesions. The cytokine assays showed that RSV could markedly decrease the production of proinflammatory mediators and cytokines (IL-1, IL-1β, IL-6, NO, iNOS and COX-2), and increase the expression of anti-inflammatory mediator (IL-10). RSV could inhibit TLR4 signaling pathway by down-regulating the mRNA levels of MyD88 and TRAF6, and suppressing the TLR4 protein. RSV could inhibit the signaling cascades of NF-κBp65 and MAPKs through down-regulating the mRNA levels of IκBα, p38MAPK, JNK, ERK1, ERK2 and ERK5 in liver and lung, and suppressing the dynamic changes of proteins and phosphorylated proteins including IκBα, NF-κBp65, p38MAPK, JNK, ERK1/2 and ERK5 from tissue’s cytoplasm to nucleus. In conclusion, RSV possessed a therapeutic effect on LPS-induced inflammation in rats and the mechanism mainly attributed to suppressing the signaling cascades of NF-κBp65 and MAPKs by inhibiting the TLR4 signaling pathway.

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“…2). This result suggested that RSV had a protective effect on LPS-induced tissue injury, which was consistent with other reports233539.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Wang

et al. 2017

Sci Rep

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“…According to the results of our previous study [25], we chose 12 h of hypoxia and 4 h of reoxygenation as the parameters for further experiments. Western blot analysis revealed that following H/R, amounts of CaMKIIα, p-TAK1, and p-IRF3 protein in KCs significantly increased, but amounts of TAK1 and IRF3 protein did not increase (Fig.…”

Section: Upregulation Of Camkiiα P-tak1 and P-irf3 In Kcs Followingmentioning

confidence: 99%

Role of miR-148a in Mitigating Hepatic Ischemia-Reperfusion Injury by Repressing the TLR4 Signaling Pathway via Targeting CaMKIIα in Vivo and in Vitro

Zheng

Wei

et al. 2018

Cell Physiol Biochem

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Background/Aims: Hepatic ischemia-reperfusion (I/R) injury, which is mainly induced by inflammation and unstable intracellular ions, is a major negative consequence of surgery that compromises hepatic function. However, the exact mechanisms of liver I/R injury have not been determined. Positive crosstalk with the Ca²⁺/CaMKII pathway is required for complete activation of the TLR4 pathway and inflammation. We previously found that miR-148a, which decreased in abundance with increasing reperfusion time, targeted and repressed the expression of CaMKIIα. In the present study, we examined the role of the miR-148a machinery in I/R-induced Ca²⁺/CaMKII and TLR4 signaling changes, inflammation, and liver dysfunction in vivo and in vitro. Methods: Liver function was evaluated by serum aminotransferase levels and hematoxylin-eosin (HE) staining. Inflammatory factors were detected by enzyme-linked immunosorbent assay. Gene and protein expression were assessed by RT-PCR and western blot. Small interfering RNA was used to silence target gene expression. HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to measure hepatic tissue apoptosis. These assays were performed to identify factors upregulated in hepatic I/R injury and downregulated by miR-148a. Results: We manifested that expression of CaMKIIα and phosphorylation of TAK1 and IRF3 were elevated in hypoxia/reoxygenation (H/R)-treated primary Kupffer cells (KCs) and liver tissue of I/R-treated mice, but these effects were attenuated by treatment with miR-148a mimic and were accompanied by the alleviation of liver dysfunction and hepatocellular apoptosis. Luciferase reporter experiments showed that miR148a suppressed luciferase activity by almost 60%. Moreover, knockdown of CaMKIIα in H/R KCs led to significant deficiencies in p-TAK1, P-IRF3, IL-6, and TNF-α, which was consistent with the effects of miR-148a overexpression. Otherwise, the same trend of activation of TAK1 and IRF3 and inflammatory factors in vitro was observed in the siTAK1 + siIRF3 group compared with the siCaMKIIα group. Conclusion: Taken together, we conclude that miR-148a may mitigate hepatic I/R injury by ameliorating TLR4-mediated inflammation via targeting CaMKIIα in vitro and in vivo.

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Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty‐two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor‐alpha, interferon‐gamma, and inteleukin‐10 [IL‐10]), mRNA expression of NF‐κB‐p65 and TLR‐4, as well as protein expression of JAK1, STAT‐3, PI3K, mTOR, Akt, and Nrf‐2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up‐regulation of NF‐κB‐p65, TLR‐4, JAK1, and STAT‐3 concomitantly with down‐regulation of Nrf‐2, IL‐10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy

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Resveratrol preconditioning protects hepatocytes against hepatic ischemia reperfusion injury via Toll-like receptor 4/nuclear factor-κB signaling pathway in vitro and in vivo

Cited by 47 publications

References 27 publications

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Resveratrol mitigates lipopolysaccharide-mediated acute inflammation in rats by inhibiting the TLR4/NF-κBp65/MAPKs signaling cascade

Role of miR-148a in Mitigating Hepatic Ischemia-Reperfusion Injury by Repressing the TLR4 Signaling Pathway via Targeting CaMKIIα in Vivo and in Vitro

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

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