Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway

Wang, Lu; Li, Ning; Lin, Dongdong; Zang, Yunjin

doi:10.18632/oncotarget.18676

Cited by 50 publications

(32 citation statements)

References 20 publications

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“…The involvement of the TLR4/NF- κ B signaling pathway in the pathogenesis of hepatic I/R injury was reported in several studies [ 13 , 36 , 56 , 57 ]. Our results revealed that the mRNA and protein expressions of hepatic TLR4 and NF- κ B were markedly elevated in the group of HIR and these results coincided with other studies [ 13 , 56 , 57 ]. The TLR4 signaling leads to the activation of the nuclear transcription factor NF- κ B which initiates the release of various numbers of proinflammatory mediators including TNF- α [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 96%

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Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Sherif

Al-Shaalan

2018

Oxidative Medicine and Cellular Longevity

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The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions.

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Section: Discussionmentioning

confidence: 96%

“…The upregulation of TLR4 was associated with the rise in TNF- α causing further liver damage and injury [ 36 , 59 ]. That is why the inhibition of the activity of the TLR4/NF- κ B signaling pathway by drugs could afford beneficial effects for the liver and presenting a potential therapy against HIR [ 13 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Sherif

Al-Shaalan

2018

Oxidative Medicine and Cellular Longevity

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“…We utilized the established non-lethal model of segmental (70%) hepatic warm ischemia/reperfusion as previously described [20]. Briefly, we anesthetized 8-week-old C57BL mice by ether inhalation and then interrupted the artery and portal venous blood supply to the left and middle liver lobes for 60 min.…”

Section: Methodsmentioning

confidence: 99%

Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

Zheng¹,

Li²,

Wei³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The present study aimed to evaluate the effects as well as the underlying mechanisms of bone marrow-derived dendritic cells (BMDCs) and exosomes produced by BMDCs (DEXs) on hepatic ischemia-reperfusion (I/R) injury (IRI). Methods: Primary hepatocytes were isolated and used to mimic the liver IR microenvironment. BMDCs were induced and characterized both biochemically with a flow cytometer (FCM) and biophysically with a microscope. Then, we exposed BMDCs to the supernatants from primary hepatocytes and evaluated the maturation of BMDCs by FCM. BMDCs were systemically injected into mice before liver IR via the tail vein, and the therapeutic effects were evaluated. The serum levels of transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT), inflammatory cytokines, and histological changes were respectively examined by ELISA, RT-qPCR and microscopy. Furthermore, we isolated DEXs by ultracentrifugation, characterized DEXs by transmission electron microscopy (TEM) and nanosight tracking analysis (NTA) and western blotting (WB), and then we co-cultured BMDCs/DEXs and naïve T cells and performed FCM, ELISA and confocal imaging. Moreover, we injected DEXs into mice prior to liver IR via the tail vein and examined its therapeutic effects by microscopy and ELISA. Finally, inhibitors of HSP70 (cmHSP70.1), PI3K (BKM120) and mTOR (Rapamycin) were used to investigate the role of HSP70 and the PI3K/mTOR axis in the effects of DEXs on naïve T cells by WB and FCM. Results: Bone marrow cells were efficiently induced into dendritic cells (DCs) with typical DC characteristics. The supernatants from primary hepatocytes exposed to H/R upregulated DC maturation markers. After DC administration, liver IR injury was improved with histopathological scores and serum transaminases. Additionally, we found that the anti-inflammatory cytokines TGF-β, Foxp3 and interleukin (IL)-10 were upregulated and that IL-17 was downregulated. Furthermore, confocal imaging revealed that the uptake of H/R-DEXs by naïve T cells was greater than that of DEXs derived from the control or negative group of BMDCs, and this increase was correlated with a significantly greater degree of differentiation of Tregs and Th17 cells. Moreover, H/R-DEXs administration improved liver function in mice after IR. Finally, the inhibition of HSP70, PI3K and mTOR completely abolished the effect of DEXs on naïve T cells. Conclusion: These results demonstrated that BMDCs and DEXs could alleviate hepatic I/R injury via modulating the balance between Tregs and Th17 cells. DEXs transported HSP70 into naïve T cells and stimulated the PI3K/mTOR axis to modulate the balance between Tregs and Th17 cells and protect the liver from IR injury.

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“…assessment of interleukin-6 (Il-6), tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) levels IL-6, TNF-α and MIP-2 levels were estimated using the previously reported methods. 45,46 Blood was collected after reperfusion for 12 h and centrifuged at 3,600× g for 15 min to gain the sera. IL-6, TNF-α and MIP-2 levels were measured using commercially available kits.…”

Section: Liver Function Assessmentmentioning

confidence: 99%

In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Fang¹,

Liu²,

Jiang³

et al. 2017

IJN

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Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly( l -lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with 1 H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles. BMP-2 could be rapidly and efficiently encapsulated through the GA-PEG-b-PLL nanocarrier under physiological conditions, exhibiting efficient encapsulation and sustained release. In addition, the GA-PEG-b-PLL-mediated BMP-2 delivery system could target the liver against hepatic diseases as it has GA-binding receptors. The anti-hepatic ischemia/reperfusion injury (anti-HI/RI) effect of BMP-2/GA-PEG-b-PLL PIC micelles was investigated in rats using free BMP-2 and BMP-2/PEG-b-PLL PIC micelles as controls, and the results showed that BMP-2/GA-PEG-b-PLL PIC micelles indicated significantly enhanced anti-HI/RI property compared to BMP-2 and BMP-2/PEG-b-PLL. All results suggested that GA-PEG-b-PLL could be used as a potential BMP-2 nanocarrier.

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Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway

Cited by 50 publications

References 20 publications

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

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