Nitric oxide pros and cons: The role of l-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat

Baky, Nayira A. Abdel; Zaidi, Zeenat F.; Fatani, Amal J.; Sayed‐Ahmed, Mohamed M.; Yaqub, Hazar

doi:10.1016/j.brainresbull.2010.07.004

Cited by 34 publications

(26 citation statements)

References 75 publications

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“…A previous study showed stronger effects with pre- than with posttreatment [18]. Also, we [19] and others [20,21,22] showed promising results with pretreatment; therefore, we chose this regimen again for the present study.…”

Section: Methodsmentioning

confidence: 89%

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Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

et al. 2015

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Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness. Degeneration of the retinal pigment epithelium (RPE) is pathognomonic for the disease, and oxidative stress plays an important role in the pathogenesis of this disease. This study investigates potential antiapoptotic and cytoprotective effects of idebenone on cultured RPE cells (ARPE-19) under conditions of oxidative stress. Methods: ARPE-19 cells were treated with 1-100 µM idebenone. Cell viability (MTT assay), induction of intracellular reactive oxygen species (ROS) and histone-associated DNA fragments in mono- and oligonucleosomes, expression of proapoptotic BAX and antiapoptotic Bcl-2 as well as senescence-associated β-galactosidase (SA-β-Gal) activity were investigated under exposure to hydrogen peroxide (H₂O₂). Results: Idebenone concentrations from 1 to 20 µM showed no toxic effects on ARPE-19 cells. When cells were treated with H₂O₂, pretreatment with 5, 7.5, 10, and 20 µM idebenone led to a significant increase in the viability of ARPE-19 cells. In addition, idebenone pretreatment significantly attenuated the induction of SA-β-Gal and intracellular ROS as well as the amount of histone-associated DNA fragments after treatment with H₂O₂. The reduction of proapoptotic BAX and the elevation of antiapoptotic Bcl-2 under idebenone show that this process is rather mediated by inhibiting H₂O₂-induced apoptosis, not necrosis. Conclusion: In this study, idebenone increased survival of ARPE-19 cells and reduced cell death, senescence, and oxidative stress by stabilizing the BAX/Bcl-2 ratio.

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Section: Methodsmentioning

confidence: 89%

“…However, many in vivo studies showed much potential of idebenone against oxidative stress in the eye [12,52,53] and other organs [13,21,54]. Antioxidants already are a major pillar of AMD therapy, but they are still not fully satisfactory.…”

Section: Discussionmentioning

confidence: 99%

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

et al. 2015

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“…The regulation in serum glucose by treatment with either agents may attributed to their ability to inhibit the production of CRP which has the major role in metabolic disturbances. Beside, quercetin was found to have hypoglycemic effect 40 , however, idebenone was reported to have a regulatory effect on energy metabolism 41 .…”

Section: Discussionmentioning

confidence: 99%

Potential Impact of Quercetin and Idebenone against Immuno- inflammatory and Oxidative Renal Damage Induced in Rats by Titanium Dioxide Nanoparticles Toxicity

et al. 2013

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“…4 IDE has been proposed to be beneficial in the treatment of neurodegenerative diseases, such as Parkinson's syndrome, Alzheimer's disease (AD), cerebral ischemia, and physiological brain aging processes. 5,6 Owing to its ability to inhibit lipid peroxidation, 4 IDE was found to induce protection from neuronal damage such as stroke, intoxication, and memory loss, and it also improves recovery after brain trauma. 7 Preliminary testing in humans reported that IDE can be regarded as a safe treatment for Friedreich's ataxia, exhibiting a positive effect on cardiac hypertrophy and neurological function.…”

Section: ■ Introductionmentioning

confidence: 99%

Idebenone Loaded Solid Lipid Nanoparticles Interact with Biomembrane Models: Calorimetric Evidence

et al. 2012

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The knowledge of the interactions between solid lipid nanoparticles (SLN) and cell membranes is important to develop effective carrier systems for drug delivery applications. Loading idebenone (IDE), an antioxidant drug useful in the treatment of neurodegenerative diseases, into SLN improves IDE antioxidant activity in in vitro biological studies, but the mechanism by which IDE permeation through the blood-brain barrier (BBB) occurs are still unclear. Therefore, in this research, unloaded and IDE loaded SLN interaction with biomembrane models, consisting of dimyristoylphosphatidylcholine multilamellar vesicles (MLV), were studied by differential scanning calorimetry (DSC). In the experiments performed, unloaded and IDE loaded SLN where incubated with the biomembrane models and their interactions were evaluated through the variations in their calorimetric curves. The results of our DSC studies indicated that the SLN under investigation were able to go inside the phospholipid bilayers with a likely localization in the outer bilayers of the MLV from where they moved toward the inner layers by increasing the contact time between SLN and MLV. Furthermore, IDE loaded SLN were able to release IDE into the biomembrane model, thus facilitating IDE penetration into the bilayers while free IDE showed only a low ability to interact with this model of biomembranes. Our results suggest that these SLN could be regarded as a promising drug delivery system to improve IDE bioavailability and antioxidant activity.

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Nitric oxide pros and cons: The role of l-arginine, a nitric oxide precursor, and idebenone, a coenzyme-Q analogue in ameliorating cerebral hypoxia in rat

Cited by 34 publications

References 75 publications

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

Idebenone Prevents Oxidative Stress, Cell Death and Senescence of Retinal Pigment Epithelium Cells by Stabilizing BAX/Bcl-2 Ratio

Potential Impact of Quercetin and Idebenone against Immuno- inflammatory and Oxidative Renal Damage Induced in Rats by Titanium Dioxide Nanoparticles Toxicity

Idebenone Loaded Solid Lipid Nanoparticles Interact with Biomembrane Models: Calorimetric Evidence

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