Colchicine attenuates renal ischemia-reperfusion-induced liver damage: implication of TLR4/NF-κB, TGF-β, and <i>BAX</i> and <i>Bcl-2</i> gene expression

Awad, Azza S.; Elariny, Hemat A.; Sallam, Amany Said

doi:10.1139/cjpp-2021-0007

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…In the current study, we selected four ABC transporter genes (Abcc2, Abcc5, Abcf2, and Abcg2) based on a literature search. All these ABC trans- porter gene are expressed in the liver and in many processes in the liver such as inflammatory response and oxidative stress (39,40). In a previous IR study on the mouse liver, Ab-cg2 and Abcc2 gene levels were decreased seven days after liver ischemia (22).…”

Section: Discussionmentioning

confidence: 98%

4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats

Güven,

Tanoglu,

Ozcelik

et al. 2023

Croat Med J

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Aim To assess the effects of 4-phenyl butyric acid (PBA) on oxidative stress, inflammation, liver histology, endoplasmic (ER) reticulum stress, and the expression levels of ATP-binding cassette transporter family members in a hepatic ischemia-reperfusion (IR) model. Methods Thirty-five rats were randomly divided into five groups: sham, IR, IR + 100 mg kg −1 PBA, IR + 200 mg kg −1 PBA, and IR + placebo. After sacrifice, we assessed serum biochemical variables, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS). The expression levels of Abcc (2 and 5), Abcg2, Abcf2, Ire1-α, and Perk genes were measured with a quantitative real-time polymerase chain reaction. ResultsSerum biochemical variables, MPO, MDA, TAS, and TOS levels of the PBA groups (especially in the low dose group) were lower than in the IR and placebo group (P < 0.05). Histological tissue damage in the IR group was more severe than in the PBA groups. Ire1-α and Perk expression levels were significantly lower in the PBA groups than the IR group (P < 0.001). Abcc (2 and 5) and Abcg2 expression levels were significantly lower in the IR group than in the sham and PBA groups (P < 0.001, P < 0.035, and P < 0.009, respectively). ConclusionsThe use of PBA significantly positively affected IR injury, which makes PBA a candidate treatment to reduce liver IR.

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Section: Discussionmentioning

confidence: 98%

4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats

Güven,

Tanoglu,

Ozcelik

et al. 2023

Croat Med J

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“…This result elucidates that ramelteon alleviates IRI by mitigating the inflammatory response. TLR4 is involved in the pathophysiology of inflammation and AKI induced by renal IRI ( 36 ). Yang et al showed that MT promotes autophagy and ameliorates renal IRI though TLR4/MyD88/MEK/ERK/mTORC1 ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Ramelteon attenuates renal ischemia and reperfusion injury through reducing mitochondrial fission and fusion and inflammation

Chen,

Liu,

Wei

2023

Transl Androl Urol

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Background Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). This study explored the function and mechanisms of ramelteon on IRI-induced AKI. Methods Mice were randomly divided into five groups: Sham, IRI, IRI + ramelteon (0.3 mg/kg), IRI + ramelteon (1 mg/kg), and IRI + ramelteon (3 mg/kg). Mice were intraperitoneally treated with ramelteon for 7 days before IRI. IRI was accomplished by bilateral renal artery clamping for 30 minutes, after which the clamps were removed for blood reperfusion. HK-2 cells were randomly divided into five groups: control, hypoxia/reoxygenation (H/R), H/R + ramelteon (10 nM), H/R + ramelteon (30 nM), and H/R + ramelteon (60 nM). HK-2 cells were prophylactically treated with ramelteon and then exposed to H/R. Results Ramelteon attenuated renal injury, inhibited cell apoptosis, decreased reactive oxygen species (ROS) generation, and suppressed levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β). Ramelteon decreased apoptosis-related protein Bax and TLR4-related proteins (TLR4, MyD88, p-IκBα, and p-p65 NF-κB), enhanced apoptosis-related protein Bcl-2. Furthermore, ramelteon increased mitochondrial membrane potential in H/R cells. Mitochondrial-related proteins (Drp1, Fis1, and Mff) were abated, whereas Mfn1 and Mfn2 were enhanced in H/R induced cells. Conclusions Ramelteon attenuates renal injury induced by IRI and H/R, which is involved in apoptosis, mitochondrial damage, and inflammation.

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“…Colchicine gel was reported to inhibit myocardial apoptosis and fibrosis in mice with myocardial infarction and improved cardiac function and structure ( Chen et al, 2020 ). Colchicine exerts its anti-inflammatory, anti-apoptotic and anti-fibrotic effects through upregulated hepatic B-cell lymphoma 2 (Bcl-2) and downregulated Bcl-2 associated X protein (BAX) expression and transforming growth factor-β (TGF-β) content, which attenuates rat liver injury induced by renal ischemia-reperfusion injury ( Awad et al, 2022 ). It was shown that when cytochrome C is released from mitochondria, it activates the caspase-3 apoptotic pathway and promotes cardiomyocyte apoptosis, making cardiac function impaired ( Radhakrishnan et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

Liu

Yin

et al. 2023

Front. Pharmacol.

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Objective: This is the first study to explore the mechanism of colchicine in treating coronary artery disease using network pharmacology and molecular docking technology, aiming to predict the key targets and main approaches of colchicine in treating coronary artery disease. It is expected to provide new ideas for research on disease mechanism and drug development.Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Swiss Target Prediction and PharmMapper databases were used to obtain drug targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DrugBank and DisGeNET databases were utilized to gain disease targets. The intersection of the two was taken to access the intersection targets of colchicine for the treatment of coronary artery disease. The Sting database was employed to analyze the protein-protein interaction network. Gene Ontology (GO) functional enrichment analysis was performed using Webgestalt database. Reactom database was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was simulated using AutoDock 4.2.6 and PyMOL2.4 software.Results: A total of 70 intersecting targets of colchicine for the treatment of coronary artery disease were obtained, and there were interactions among 50 targets. GO functional enrichment analysis yielded 13 biological processes, 18 cellular components and 16 molecular functions. 549 signaling pathways were obtained by KEGG enrichment analysis. The molecular docking results of key targets were generally good.Conclusion: Colchicine may treat coronary artery disease through targets such as Cytochrome c (CYCS), Myeloperoxidase (MPO) and Histone deacetylase 1 (HDAC1). The mechanism of action may be related to the cellular response to chemical stimulus and p75NTR-mediated negative regulation of cell cycle by SC1, which is valuable for further research exploration. However, this research still needs to be verified by experiments. Future research will explore new drugs for treating coronary artery disease from these targets.

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Colchicine attenuates renal ischemia-reperfusion-induced liver damage: implication of TLR4/NF-κB, TGF-β, and BAX and Bcl-2 gene expression

Cited by 9 publications

References 41 publications

4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats

4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats

Ramelteon attenuates renal ischemia and reperfusion injury through reducing mitochondrial fission and fusion and inflammation

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

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