Olprinone protects the liver from ischemia–reperfusion injury through oxidative stress prevention and protein kinase Akt activation

Béjaoui, Mohamed; Zaoualí, Mohamed Amine; Sakly, Rim; Abdennebi, Hassen Ben

doi:10.1139/cjpp-2017-0153

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…The latest studies demonstrated the efficacy of cilostazol in alopecia, Down syndrome, and allergic diseases, rendering cilostazol a multipurpose drug. Meanwhile, olprinone was proven to reduce liver ischemia-reperfusion injury by preventing oxidative stress and activating PKA . It was additionally evaluated as a possible therapy for acute respiratory distress syndrome (ARDS) …”

Section: Dual-specific Pdesmentioning

confidence: 99%

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Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

et al. 2021

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Cyclic nucleotide phosphodiesterases (PDEs) control the intracellular concentrations of cAMP and cGMP in virtually all mammalian cells. Accordingly, the PDE family regulates a myriad of physiological functions, including cell proliferation, differentiation and apoptosis, gene expression, central nervous system function, and muscle contraction. Along this line, dysfunction of PDEs has been implicated in neurodegenerative disorders, coronary artery diseases, chronic obstructive pulmonary disease, and cancer development. To date, 11 PDE families have been identified; however, their distinct roles in the various pathologies are largely unexplored and subject to contemporary research efforts. Indeed, there is growing interest for the development of isoform-selective PDE inhibitors as potential therapeutic agents. Similarly, the evolving knowledge on the various PDE isoforms has channeled the identification of new PET probes, allowing isoform-selective imaging. This review highlights recent advances in PDE-targeted PET tracer development, thereby focusing on efforts to assess disease-related PDE pathophysiology and to support isoform-selective drug discovery.

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Section: Dual-specific Pdesmentioning

confidence: 99%

“…Meanwhile, olprinone was proven to reduce liver ischemia-reperfusion injury by preventing oxidative stress and activating PKA. 148 It was additionally evaluated as a possible therapy for acute respiratory distress syndrome (ARDS). 149 PDE10Overview: Structure and Distribution.…”

Section: ■ Introductionmentioning

confidence: 99%

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

et al. 2021

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“…Akt activation promotes phosphorylation of downstream molecules, including the apoptosis-related family members of Bcl2, the mammalian target of rapamycin (mTOR), glycogen synthase kinase-3 (GSK3) and various transcription factors [ 15 , 16 ]. Therefore, numerous publications reported that Akt activation mediates the beneficial effects of the tested compounds as well as in brain, heart, kidney and liver ischemia [ 17 , 18 , 19 , 20 , 21 ]. Several ischemic preconditioning protocols, which consist of applying brief repetition of artery occlusion and reperfusion steps, have been described as efficient for ischemic organ protection especially during transplantation [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia

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Carcy

Rubera

et al. 2021

IJMS

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Lesions issued from the ischemia/reperfusion (I/R) stress are a major challenge in human pathophysiology. Of human organs, the kidney is highly sensitive to I/R because of its high oxygen demand and poor regenerative capacity. Previous studies have shown that targeting the hypusination pathway of eIF5A through GC7 greatly improves ischemic tolerance and can be applied successfully to kidney transplants. The protection process correlates with a metabolic shift from oxidative phosphorylation to glycolysis. Because the protein kinase B Akt is involved in ischemic protective mechanisms and glucose metabolism, we looked for a link between the effects of GC7 and Akt in proximal kidney cells exposed to anoxia or the mitotoxic myxothiazol. We found that GC7 treatment resulted in impaired Akt phosphorylation at the Ser473 and Thr308 sites, so the effects of direct Akt inhibition as a preconditioning protocol on ischemic tolerance were investigated. We evidenced that Akt inhibitors provide huge protection for kidney cells against ischemia and myxothiazol. The pro-survival effect of Akt inhibitors, which is reversible, implied a decrease in mitochondrial ROS production but was not related to metabolic changes or an antioxidant defense increase. Therefore, the inhibition of Akt can be considered as a preconditioning treatment against ischemia.

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“…[6][7][8] Therefore, it is important to maintain the oxidant/ antioxidant balance and hemostatic defense mechanisms in antioxidant-depleted LDLT recipients by supplying exogenous antioxidants. [9][10][11] In particular, ascorbic acid (AA, vitamin C), a water soluble and essential micronutrient, is a biologically important cofactor for biosynthetic enzymes and a potent antioxidant, which can play an important role in hemostatic defense against oxidative stress. 12 AA can have broad effects on the coagulation pathway, from the initiation of coagulation to fibrinolysis.…”

Section: Introductionmentioning

confidence: 99%

Ascorbic acid improves thrombotic function of platelets during living donor liver transplantation by modulating the function of the E3 ubiquitin ligases c-Cbl and Cbl-b

et al. 2019

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Objective To investigate the effect of ascorbic acid (AA) on hemostatic function during living donor liver transplantation (LDLT). Methods Blood samples from 21 LDLT recipients were taken within 30 minutes after induction and at 120 minutes after reperfusion. Rotational thromboelastography (TEG) and western blot analysis were used to analyze for fibrinolysis and functional changes in c-Cbl and Cbl-b, respectively. TEG test samples were prepared as one of three groups: C group (0.36 mL of blood), N group (0.324 mL of blood + 0.036 mL of 0.9% normal saline), and A group (0.324 mL of blood + 0.036 mL of 200 µmol/L-AA dissolved in 0.9% normal saline). Results AA decreased fibrinolysis and increased clot rigidity at baseline and 120 minutes after reperfusion. Cbl-b expression was significantly increased at baseline and 120 minutes after reperfusion in the A group compared with the C and N groups. However, c-Cbl phosphorylation was most significantly decreased in the A group at baseline and 120 minutes after reperfusion. Conclusion AA can significantly decrease fibrinolysis and improve clot rigidity in LT recipients during LDLT, and functional changes in Cbl-b and c-Cbl might represent the underlying mechanism. AA may be considered for use during LDLT to decrease hyperfibrinolysis.

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Olprinone protects the liver from ischemia–reperfusion injury through oxidative stress prevention and protein kinase Akt activation

Cited by 8 publications

References 37 publications

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery

Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia

Ascorbic acid improves thrombotic function of platelets during living donor liver transplantation by modulating the function of the E3 ubiquitin ligases c-Cbl and Cbl-b

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