Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium

Mokhtari, Behnaz; Badalzadeh, Reza; Alihemmati, Alireza; Mohammadi, Mustafa

doi:10.1016/j.ejphar.2015.08.056

Cited by 38 publications

(37 citation statements)

References 32 publications

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“…Troxerutin has protective effects in several tissues, including kidney [16], liver [17] and brain [18]. In the context of myocardial I/R injury, troxerutin has a protective effect against reperfusion injury of diabetic myocardium by attenuating GSK-3β activity and subsequently reducing apoptosis [19]. The PI3K/Akt pathway is important in mediating the effect of troxerutin [20].…”

Section: Introductionmentioning

confidence: 99%

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Shu

Zhang

Huang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. Methods: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. Results: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3) also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. Conclusion: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway.

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Section: Introductionmentioning

confidence: 99%

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Shu

Zhang

Huang

et al. 2017

Cell Physiol Biochem

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“…It is comprised of two isoforms (α and β) which are encoded by distinct genes and are ubiquitously expressed. Numerous studies have shown that GSK-3β, but not GSK-3α is cardioprotective [9,10]. …”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

Zuo¹,

Wang²,

Hu³

et al. 2016

Cell Physiol Biochem

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Objective: This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Method: Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Results: Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. Conclusion: These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.

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“…[1314] The tissue protective effects of troxerutin in kidney,[15] liver,[16] and brain[17] injuries have been reported in previous studies. We previously reported that it prevents diabetic vascular abnormalities through the reduction of lipid peroxidation and improvement of endogenous antioxidative activity.…”

mentioning

confidence: 87%

Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats

et al. 2016

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Objectives:Inflammation plays a critical role in the progression of diabetic complications such as neurological disorders. Previous reports have indicated the memory-improving effect of troxerutin, in rat hippocampus, but the underlying mechanisms are unclear. Hence, we have investigated the effect of troxerutin pretreatment on gene expressions of inflammation-related microRNAs (miRs), miR-146a and miR-155, and nuclear factor-kappa B (NF-κB) signaling pathway in the hippocampus of healthy and diabetic rats.Materials and Methods:Wistar rats were randomly divided into four groups (control, control + troxerutin, diabetic, and diabetic + troxerutin). Diabetes was induced by a single i.p. injection of streptozotocin (50 mg/kg). Troxerutin (150 mg/kg) was orally administered in animals for 1 month. After 10 weeks of diabetes, animals were anesthetized and decapitated for the isolation of hippocampus. The expression of miR-146a and miR-155 and the messenger RNA (mRNA) expressions of NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were analyzed by real-time polymerase chain reaction.Results:Diabetes significantly increased hippocampal mRNA levels of NF-κB, IRAK-1, and TRAF-6 compared with nondiabetic rats (P < 0.05); however, pretreatment with troxerutin decreased them in both diabetic and nondiabetic animals, independent of its glycemic effect (P < 0.05). The expression levels of miR-146a and miR-155 were decreased in diabetic group as compared to the control (P < 0.01).Conclusion:These findings showed that troxerutin could inhibit the inflammatory NF-κB pathway in the hippocampus of diabetic rats, which may be due to the negative feedback loop regulated by miR-146a.

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Phosphorylation of GSK-3β and reduction of apoptosis as targets of troxerutin effect on reperfusion injury of diabetic myocardium

Cited by 38 publications

References 32 publications

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats

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