Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats

Tekin, Suat; Beytur, A.; Çakır, Murat; Taşlidere, Aslı; Erden, Yavuz; Tekin, Çiğdem; Sandal, Süleyman

doi:10.1080/13813455.2020.1715442

Cited by 11 publications

(9 citation statements)

References 49 publications

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“…Several studies elucidated that oxidative stress, inflammatory response, and apoptotic cell death are the main interrelated factors contributing to AKI after exposure to IRI in surgeries, like those of kidney transplantation. [4,7,8] Meanwhile, vinpocetine has been reported to alleviate oxidative damage, inflammation, and renal cell death after AKI. [21,39] Therefore, the present study was conducted to investigate the in vivo antioxidant, anti-inflammatory, and antiapoptotic effects of vinpocetine against renal IRI through modulation of Nrf2/NADPH oxidase, IKKβ/NF-κB p65, and caspase-3 expressions.…”

Section: Discussionmentioning

confidence: 99%

“…The second phase is the phase of re-oxygenation which triggers reactive oxygen species (ROS) production, inflammatory cascade propagation, and renal tubular damage. [7,8] Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is an important transcription regulator that has been involved in the pathogenesis of renal IRI through the production of proinflammatory cytokines, and the regulation of renal cell apoptosis. [9,10] Interestingly, activation of NF-κB is regulated by two types of proteins; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα) and IκB kinase (IKK), which are extremely important in the regulation of NF-κB activation and translocation.…”

Section: Introductionmentioning

confidence: 99%

“…The second phase is the phase of re‐oxygenation which triggers reactive oxygen species (ROS) production, inflammatory cascade propagation, and renal tubular damage. [ 7,8 ]…”

Section: Introductionmentioning

confidence: 99%

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Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

Azouz

Hersi

Ali

et al. 2022

J Biochem & Molecular Tox

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Ischemia/reperfusion injury (IRI) during kidney transplantation is a serious clinical problem with a high mortality rate and a lack of therapy. Therefore, there is a need to improve the ability of the kidney to tolerate IRI during transplantation. This study aimed to investigate the possible protective effect of vinpocetine; a derivative of vincamine alkaloid; against renal IRI in rats with the elucidation of the involved mechanisms. Vinpocetine (25 mg/kg; i.p.) was administered for 10 successive days before the induction of ischemia by bilateral clamping of both renal pedicles for 45 min followed by 24 h of reperfusion. Blood and renal tissue samples were then collected for biochemical, molecular, and histopathological investigations. Vinpocetine significantly reduced serum creatinine and blood urea nitrogen levels in rats subjected to IRI. It also reduced mRNA expression of NADPH oxidase and renal content of malondialdehyde, while enhanced Nrf2 protein expression and renal content of reduced glutathione. The suppression of the provoked inflammatory response was evident by the downregulation of IKKβ and NF‐κB p65 protein expressions, as well as their downstream inflammatory markers; tumor necrosis factor‐α, interleukin‐6, and myeloperoxidase. In addition, vinpocetine reduced protein expression of the apoptotic executioner cleaved caspase‐3. These nephroprotective effects were confirmed by the improvement in histopathological features. Collectively, the protective effect of vinpocetine against IRI could be attributed to modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions. Thus, vinpocetine could improve oxidant/antioxidant balance, suppress triggered inflammatory response, and promote renal cell survival after IRI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

Azouz

Hersi

Ali

et al. 2022

J Biochem & Molecular Tox

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“…Recently, ferroptosis has been reported to be involved in I/R injury in the kidney [ 21 ]. I/R injury in the kidney occurs in two phases [ 61 , 62 ]: the ischemic phase, which is the phase of renal tissue de-oxygenation and ATP depletion, and the re-oxygenation phase that triggers ROS production, inflammatory cascade propagation, and renal tubular damage. Both phases are involved in ferroptosis.…”

Section: The Role Of Ferroptosis In Akimentioning

confidence: 99%

Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury

Hosohata

Harnsirikarn

Chokesuwattanaskul

2022

IJMS

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Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.

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“…During the ischaemic phase, the hypoxic state initiates vasodilation and increased microvascular permeability. At the onset of reperfusion, a vast amount of reactive oxygen species (ROS) are generated 1 . The elevated ROS target and damage to the functional cellular components can predispose to cell death 2 .…”

Section: Introductionmentioning

confidence: 99%

Necrostatin‐1 mitigates renal ischaemia–reperfusion injury ‐ time dependent ‐ via aborting the interacting protein kinase (RIPK‐1)‐induced inflammatory immune response

Ashour

Hashem

Khowailed

et al. 2022

Clin Exp Pharma Physio

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The recently defined necroptosis process participates in the pathophysiology of several tissue injuries. Targeting the necroptosis mediator receptor‐interacting protein kinase (RIPK1) by necrostatin‐1 in different phases of ischaemia–reperfusion injury (IRI) may provide new insight into the protection against renal IRI. The rat groups included (n = 8 in each group): 1) Sham; 2) Renal IRI; 3) Necrostatin‐1 treatment 20 min before ischaemia induction in a dose of 1.65 mg/kg/intravenous; 4) Necrostatin‐1 injection just before reperfusion; 5) Necrostatin‐1 injection 20 min after reperfusion establishment; and 6) drug injection at both the pre‐ischaemia and at reperfusion time in the same dose. Timing dependent, necrostatin‐1 diminished RIPK1 (p < 0.001), and aborted the necroptosis‐induced renal cell injury. Necrostatin‐1 decreased the renal chemokine (CXCL1), interleukin‐6, intercellular adhesion molecule (ICAM‐1), myeloperoxidase, and the nuclear factor (NFκB), concomitant with reduced inducible nitric oxide synthase (iNOS), inflammatory cell infiltration, and diminished cell death represented by apoptotic cell count and the BAX/Bcl2 protein ratio. In group 6, the cell injury was minimal and the renal functions (creatinine, BUN and creatinine clearance) were almost normalised. The inflammatory markers were diminished (p < 0.001) compared to the IRI group. The results were confirmed by histopathological examination. In conclusion, RIPK1 inhibition ameliorates the inflammatory immune response induced by renal IRI. The use of two doses was more beneficial as the pathophysiology of cell injury is characterised.

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Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats

Cited by 11 publications

References 49 publications

Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury

Necrostatin‐1 mitigates renal ischaemia–reperfusion injury ‐ time dependent ‐ via aborting the interacting protein kinase (RIPK‐1)‐induced inflammatory immune response

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