Investigation of the Effect of Milrinone on Renal Damage in an Experimental Non-Heart Beating Donor Model

Uysal, Erdal; Dokur, Mehmet; Altınay, Serdar; Saygılı, Eyüp İlker; Batçıoğlu, Kadir; Ceylan, Seyit Mehmet; Kazımoğlu, Hatem; Uyumlu, Burcin; Karadağ, Mehmet

doi:10.1080/08941939.2017.1343880

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…These data concur with a previous study showing that a high concentration of forskolin caused cellular apoptosis (Paschoal et al, 2016). Conversely, other studies found that Mil suppresses cell apoptosis in some organ-injured animal models (Ceylan et al, 2019;Oikawa et al, 2013;Uysal et al, 2018). In bovine models, Milmediated meiotic progression delay does not increase oocyte apoptosis (Dall'Acqua, Leao, Rocha-Frigoni, Gottardi, & Mingoti, 2017).…”

Section: Discussionsupporting

confidence: 91%

Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes

Han

Hao

et al. 2020

Molecular Reproduction Devel

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Phosphodiesterase (PDE)‐mediated reduction of cyclic adenosine monophosphate (cAMP) activity can initiate germinal vesicle (GV) breakdown in mammalian oocytes. It is crucial to maintain oocytes at the GV stage for a long period to analyze meiotic resumption in vitro. Meiotic resumption can be reversibly inhibited in isolated oocytes by cAMP modulator forskolin, cAMP analog dibutyryl cAMP (dbcAMP), or PDE inhibitors, milrinone (Mil), Cilostazol (CLZ), and 3‐isobutyl‐1‐methylxanthine (IBMX). However, these chemicals negatively affect oocyte development and maturation when used independently. Here, we used ICR mice to develop a model that could maintain GV‐stage arrest with minimal toxic effects on subsequent oocyte and embryonic development. We identified optimal concentrations of forskolin, dbcAMP, Mil, CLZ, IBMX, and their combinations for inhibiting oocyte meiotic resumption. Adverse effects were assessed according to subsequent development potential, including meiotic resumption after washout, first polar body extrusion, early apoptosis, double‐strand DNA breaks, mitochondrial distribution, adenosine triphosphate levels, and embryonic development. Incubation with a combination of 50.0 μM dbcAMP and 10.0 μM IBMX efficiently inhibited meiotic resumption in GV‐stage oocytes, with low toxicity on subsequent oocyte maturation and embryonic development. This work proposes a novel method with reduced toxicity to effectively arrest and maintain mouse oocytes at the GV stage.

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Section: Discussionsupporting

confidence: 91%

Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes

Han

Hao

et al. 2020

Molecular Reproduction Devel

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“…Using an ex‐vivo model of the human myocardium, Usta et al assessed the ischaemia‐reperfusion injury that occurred after cardioplegia and reported that milrinone strongly suppressed the apoptosis (Usta et al., 2010). In their study assessing the efficacy of milrinone on renal damage based on the experimental nonheart beating donor model, Uysal et al found that this pharmacological agent showed antioxidant efficacy by resulting in an increase in SOD and GSH‐Px levels after ischaemia‐reperfusion injury and additionally lowered the apoptotic index in renal tubules and glomerular cells and thus collectively contributed to renoprotective properties (Uysal et al., 2018). Similarly, Raupach et al showed that milrinone possessed cardioprotective activity by minimising the ROS level (Raupach et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, tumour necrosis factor‐alpha (TNF‐alpha) levels decrease to very low levels as the cAMP level increases. Inflammation is suppressed and apoptosis is decreased due to these dramatic changes in TNF‐alpha levels (Uysal et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, tumour necrosis factor-alpha (TNF-alpha) levels decrease to very low levels as the cAMP level increases. Inflammation is suppressed and apoptosis is decreased due to these dramatic changes in TNF-alpha levels (Uysal et al, 2018). This experimental study was designed to determine the possible protective effect of milrinone against oxidative stress due to testicular torsion/detorsion.…”

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confidence: 99%

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Milrinone ameliorates ischaemia‐reperfusion injury in experimental testicular torsion/detorsion rat model

et al. 2021

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This experimental study aims to evaluate the efficacy of milrinone against ischaemia‐reperfusion injury due to testicular torsion/detorsion. Group 1 was defined as the control group. Testicular torsion/detorsion model was performed in Group 2. Group 3 had similar procedures to the rats in Group 2. In addition, 0.5 mg/kg of milrinone was administered intraperitoneally immediately after testicular torsion in Group 3. Histopathological examinations indicated a dramatic improvement in terms of inflammation, haemorrhage, oedema, congestion, Cosentino and Johnson scores in Group 3 compared to Group 2 (p = .037, p = .045, p = .018, p = .040, p = .033 and p = .03 respectively). Blood biochemical analyses, superoxide dismutase (SOD), glutathione peroxidase (GSH‐px) activity and total antioxidant status (TAS) levels increased significantly in Group 3 compared to Group 2 (p = .001, p = .024 and p < .001). Malondialdehyde (MDA), protein carbonyl (PC), interleukin 1beta (IL‐1beta), tumour necrosis factor‐alpha (TNF‐alpha) and total oxidant status (TOS) levels decreased in Group 3 compared to Group 2 (p = .001, p = .018, p < .001, p = .036 and p = .002 respectively). Tissue biochemical analyses determined an increase in SOD and GSH‐px activity in Group 3 compared to Group 2, while PC and MDA levels were reduced (p = .001, p < .001, p = .038 and p < .001 respectively). Milrinone attenuates ischaemia‐reperfusion injury that causes highly harmful effects due to testicular torsion/detorsion.

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“…Moreover, several studies demonstrated that milrinone has the capability to decrease apoptosis and release free oxygen radicals, with a consequent anti-inflammatory effect [10][11][12]. Vasodilatation, anti-inflammatory and antiaggregant effects of milrinone on regulating microcirculation cause an increase of tissue perfusion [13].…”

Section: Introductionmentioning

confidence: 99%

Development of a Rapid Mass Spectrometric Determination of AMP and Cyclic AMP for PDE3 Activity Study: Application and Computational Analysis for Evaluating the Effect of a Novel 2-oxo-1,2-dihydropyridine-3-carbonitrile Derivative as PDE-3 Inhibitor

et al. 2020

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A simple, quick, easy and cheap tandem mass spectrometry (MS/MS) method for the determination of adenosine monophosphate (AMP) and cyclic adenosine monophosphate (cAMP) has been newly developed. This novel MS/MS method was applied for the evaluation of the inhibitory effect of a novel 2-oxo-1,2-dihydropyridine-3-carbonitrile derivative, also named DF492, on PDE3 enzyme activity in comparison to its parent drug milrinone. Molecule DF492, with an IC 50 of 409.5 nM, showed an inhibition of PDE3 greater than milrinone (IC 50 = 703.1 nM). To explain the inhibitory potential of DF492, molecular docking studies toward the human PDE3A were carried out with the aim of predicting the binding mode of DF492. The presence of different bulkier decorating fragments in DF492 was pursued to shift affinity of this novel molecule toward PDE3A compared to milrinone in accordance with both the theoretical and experimental results. The described mass spectrometric approach could have a wider potential use in kinetic and biomedical studies and could be applied for the determination of other phosphodiesterase inhibitor molecules.

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Investigation of the Effect of Milrinone on Renal Damage in an Experimental Non-Heart Beating Donor Model

Cited by 8 publications

References 47 publications

Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes

Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes

Milrinone ameliorates ischaemia‐reperfusion injury in experimental testicular torsion/detorsion rat model

Development of a Rapid Mass Spectrometric Determination of AMP and Cyclic AMP for PDE3 Activity Study: Application and Computational Analysis for Evaluating the Effect of a Novel 2-oxo-1,2-dihydropyridine-3-carbonitrile Derivative as PDE-3 Inhibitor

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