Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury?

Tuncer, Sema; Akkoca, Ahmet; Celen, Murat Cenk; Dalkılıç, Nizamettin

doi:10.1007/s00210-020-02039-1

Cited by 8 publications

(5 citation statements)

References 38 publications

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“…Tempo (4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl) is a cell‐permeable synthetic cyclic nitroxide compound that reduces the intracellular ROS, subsequently protect the cells and tissues from oxidative injuries 31 . Mito‐TEMPO is a modified form of Tempo with triphenylphosphonium that directly targets mitochondria 32 . EUK‐134 and EUK‐8 are salen Mn, synthetic superoxide dismutase (SOD)/catalase mimetics that have beneficial effects in many models of oxidative stress is an antioxidant with powerful SOD, catalase and oxyradical scavenging property 33 (Figure 1A,a–d).…”

Section: Resultsmentioning

confidence: 99%

“…31 Mito-TEMPO is a modified form of Tempo with triphenylphosphonium that directly targets mitochondria. 32 EUK-134 and EUK-8 are F I G U R E 2 Molecular docking studies between HSF-, NN-PLA 2 with EUK-8: Energetically favorable binding modes of EUK-8 was calculated using induced fit molecular docking method. The hydrogen bonding and hydrophobic interactions between the EUK-8 with HSF-PLA 2 and NN-PLA 2 are depicted using the LigPlot software.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Jayachandra

Gowda

Rudresha

et al. 2022

J of Cellular Biochemistry

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The arachidonic acid (AA) metabolic pathway, plays a vital role in the production of eicosanoids by the action of pro-inflammatory secretory phospholipase A 2 (PLA 2 ). Release of eicosanoids is known to be involved in many inflammatory diseases. Identification of the inhibitory molecules of this AA pathway enzyme along with the regulation of intracellular signaling cascades may be a finer choice to develop as a powerful anti-inflammatory drug. In this regard, we have screened few cell-permeable antioxidant molecules Tempo, Mito-TEMPO, N,N'-Bis (salicylideneamino)ethane-manganese(II) (EUK)-134, and EUK-8 against proinflammatory sPLA 2 s. Among these, we found EUK-8 is a potent inhibitor with its IC 50 value ranges 0.7-2.0 µM for sPLA 2 s isolated from different sources.Furthermore, docking studies confirm the strong binding of EUK-8 towards sPLA 2 . In vivo effect of EUK-8 was studied in HSF-sPLA 2 -induced edema in mouse paw model. In addition to neutralizing the edema, EUK-8 significantly reduces the phosphorylation level of inflammatory proteins such as p38 member of MAPK pathway, Akt, and p65 along with the suppression of pro-inflammatory cytokine (interleukin-6) and chemokine (CXCL1) in edematous tissue. This shows that EUK-8 not only inhibits the sPLA 2 activity, it also plays an important role in the regulation of sPLA 2 -induced cell signaling cascades. Apart from the sPLA 2 inhibition, we also examine the regulatory actions of EUK-8 with other downstream enzymes of AA pathway such as 5-LOX assay in human polymorphonuclear leukocytes (PMNs) and COX-2 expression in carrageenan-λ induced paw edema. Here EUK-8 significantly inhibits 5-LOX enzyme activity and downregulates COX-2 expression. These data indicate that EUK-8 found to

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Jayachandra

Gowda

Rudresha

et al. 2022

J of Cellular Biochemistry

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“…There are studies from other research groups in various pathologies, as well as from our laboratory in ischemia-reperfusion injury, demonstrating therapeutic and/or protective effects of MitoTEMPO when applied at a dose of 0.7 mg/kg/day [28][29][30][31]. Therefore, this dose has been chosen in the current study.…”

Section: Nerve Dissection and Experimental Setupmentioning

confidence: 99%

Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis

Celen,

Akkoca,

Tuncer

et al. 2023

Biomedicines

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Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis. Peripheral nerve injuries often result in long-lasting functional deficits, prompting the need for effective interventions. MitoTEMPO (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride) is a mitochondria-targeted antioxidant that has shown protective and therapeutic effects against pathologies associated with reactive oxygen species. This study explores the utilization of MitoTEMPO as a therapeutic and protective agent for sciatic nerve crush injuries. By employing advanced mathematical approaches, the study seeks to comprehensively analyze nerve conduction parameters, nerve excitability, and the distribution of nerve conduction velocities to gauge the potential. Forty Wistar-Albino rats were randomly divided into following groups: (I) SHAM—animals subjected to sham operation and treated intraperitoneally (i.p.) with vehicle (bidistilled water) for 14 days; (II) CI (crush injury)—animals subjected to CI and treated with vehicle 14 days; (III) MiP—animals subjected to 7 days i.p. MitoTEMPO treatment before CI (0.7 mg/kg/day dissolved in vehicle) and, only vehicle for 7 days after CI, protective MitoTEMPO; and (IV) MiT—animals i.p. treated with only vehicle for 7 days before CI and 7 days with MitoTEMPO (0.7 mg/kg/day dissolved in vehicle) after CI, therapeutic MitoTEMPO. Nerve excitability parameters were measured, including rheobase and chronaxie, along with compound action potential (CAP) recordings. Advanced mathematical analyses were applied to CAP recordings to determine nerve conduction velocities and distribution patterns. The study revealed significant differences in nerve excitability parameters between groups. Nerve conduction velocity was notably reduced in the MiP and CI groups, whereas CAP area values were diminished in the MiP and CI groups compared to the MiT group. Furthermore, CAP velocity was lower in the MiP and CI groups, and maximum depolarization values were markedly lower in the MiP and CI groups compared to the SHAM group. The distribution of nerve conduction velocities indicated alterations in the composition of nerve fiber groups following crush injuries. In conclusion, postoperative MitoTEMPO administration demonstrated promising results in mitigating the detrimental effects of nerve crush injuries.

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“…In addition, SS31 accumulates in the mitochondrial membrane to protect and restore the mitochondrial structure without affecting healthy mitochondria (162,(447)(448)(449)(450)(451)(452)(453). Thus, SS31 and mitoTEMPO have protective effects on a variety of diseases, including heart and kidney-related diseases, as well as sepsis and diabetes, which have been demonstrated in a variety of animal models (454)(455)(456)(457). The use of nanomaterials for mitochondrial targeting therapy has become a recent focus of research.…”

Section: Mitochondrialmentioning

confidence: 99%

Common methods in mitochondrial research (Review)

Yin

Shen

2022

Int J Mol Med

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Mitochondrial abnormalities are primarily seen in morphology, structure and function. They can cause damage to organs, including the heart, brain and muscle, by various mechanisms, such as oxidative stress, abnormal energy metabolism, or genetic mutations. Identifying and detecting pathophysiological alterations in mitochondria is the principal means of studying mitochondrial abnormalities. The present study reviewed methods in mitochondrial research and focused on three aspects: Mitochondrial extraction and purification, morphology and structure and function. In addition to classical methods, such as electron microscopy and mitochondrial membrane potential monitoring, newly developed methods, such as mitochondrial ultrastructural determination, mtdNA mutation assays, metabolomics and analyses of regulatory mechanisms, have also been utilized in recent years. These approaches enable the accurate detection of mitochondrial abnormalities and provide guidance for the diagnosis and treatment of related diseases. Contents1. Introduction 2. Extraction and purification of mitochondria 3. determination of mitochondrial morphology and structure 4. determination of mitochondrial function 5.

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Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury?

Cited by 8 publications

References 38 publications

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis

Common methods in mitochondrial research (Review)

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Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury?

Cited by 8 publications

References 38 publications

Inhibition of sPLA2 enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA2 in inflammatory mouse paw edema model

Inhibition of sPLA2 enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA2 in inflammatory mouse paw edema model

Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis

Common methods in mitochondrial research (Review)

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Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model