Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Villegas-Rivera, Geannyne; Román-Pintos, Luis Miguel; Cardona-Muñoz, Ernesto Germán; Arias-Carvajal, Óscar; Rodríguez-Carrizález, Adolfo Daniel; Troyo-Sanromán, Rogelio; Pacheco-Moisés, Fermín Paul; Moreno‐Ulloa, Aldo; Miranda-Díaz, Alejandra Guillermina

doi:10.1155/2015/756294

Cited by 43 publications

(25 citation statements)

References 36 publications

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“…The results of a 5-year follow-up demonstrated that statins have a beneficial effect on the incidence of neuropathy, with a hazard ratio (HR) of 0.65 (CI 95% 0.46–0.93) [134]. Ezetimibe/Simvastatin and Rosuvastatin have been shown to reduce LPO after 16 weeks of treatment in type 2 DM patients with DPN, although no clinical outcomes were drastically changed compared to placebo [135]. However, a study performed in coronary artery disease patients where Ezetimibe/Simvastatin 10/20 mg was compared to Simvastatin 80 mg as monotherapy demonstrated that inflammation biomarkers (CRP, IL-6, monocyte chemoattractant protein-1, and soluble CD40) were unaltered after 6 weeks of treatment, probably explained by the theory that the target of statins resides on oxidative stress rather than inflammatory response [136].…”

Section: Diabetic Polyneuropathymentioning

confidence: 99%

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Román-Pintos

Villegas-Rivera

Rodríguez-Carrizález

et al. 2016

Journal of Diabetes Research

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Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

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Section: Diabetic Polyneuropathymentioning

confidence: 99%

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Román-Pintos

Villegas-Rivera

Rodríguez-Carrizález

et al. 2016

Journal of Diabetes Research

Self Cite

173

153

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“…550475; BD Biosciences, San Jose, CA, USA). A total of 5 µl Annexin V-FITC and 5 µl propidium iodide were added to SH-SY5Y cells (~2x10 5 ) that were treated with Naphthoflavone and incubated at room temperature for 15 min in the dark. The extent of apoptosis was analyzed with a dual laser FACSCalibur flow cytometer (BD Biosciences) and estimated using the ModFit LT™ software version 2.0 (Verity Software House, Topsham, ME, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The implication of OS in neurological diseases is associated with its effect on neurocytes; the structural and functional characteristics present in neurocytes include easily peroxidizable unsaturated fatty acids, high oxygen consumption rate and relative paucity of antioxidant enzymes, resulting in the vulnerability of neurocytes to OS (2). Furthermore, the incidence of OS and the opportunity of neurocytes exposed to OS are increased by exposure to environmental toxins (3), deficient antioxidants present in the diet source (4) and pathological conditions such as diabetes (5). An increase in OS is caused by excessive production of oxidative radical species (ROS), leading to the endogenous antioxidant defenses being overwhelmed (6).…”

Section: Introductionmentioning

confidence: 99%

α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage

Zhu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Previous studies have demonstrated an association between neurological diseases and oxidative stress (OS).Naphthoflavone is a synthetic derivative of naturally occurring flavonoids that serves an important role in the treatment and prevention of OS-related diseases. The current study was designed to apply α-and β-Naphthoflavone individually and in combination to counteract the detrimental effects of OS on neurons in vitro. Neuronal SH-SY5Y cells were subjected to 20 µM H 2 O 2 , followed by exposure to 20 µM α-Naphthoflavone and/or 10 µM β-Naphthoflavone. Results indicated that α-and β-Naphthoflavone effectively antagonized the apoptosis-promoting effect of H 2 O 2 on neuronal SH-SY5Y cells, and that β-Naphthoflavone significantly (P<0.05) reversed H 2 O 2 -inhibited cell viability. Notably, co-treatment of α-and β-Naphthoflavone reversed the H 2 O 2 -induced apoptosis rate elevation and cell viability reduction. Further analysis demonstrated that H 2 O 2 inhibited the activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase, but this was reversed by the co-treatment with α-and β-Naphthoflavone and selectively enhanced by the treatment with α-or β-Naphthoflavone. H 2 O 2 -stimulated p38 mitogen-activated protein kinase activation was repressed following treatment with α-and/or β-Naphthoflavone, along with a decreased expression of the apoptosis-related factors and inhibited caspase-3 activation. In conclusion, co-treatment with α-and β-Naphthoflavone minimized H 2 O 2 -led neuron damage compared with treatment with α-or β-Naphthoflavone, suggesting a synergetic effect between α-and β-Naphthoflavone. This indicates that utilizing α-and β-Naphthoflavone together in the clinical setting may provide a novel therapeutic for neurological disease.

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“…The literature search yielded 1,301 citations, and we identified 13 studies that investigated the association between cholesterollowering medication use and polyneuropathy. [1][2][3][4][22][23][24][25][26][27][28][29][30] These studies showed conflicting results, and do not provide sufficient evidence that cholesterol-lowering medication use is a risk factor for polyneuropathy. A review of the literature is given in table 1.…”

Section: Literature Reviewmentioning

confidence: 99%

Statins do not increase risk of polyneuropathy

et al. 2019

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Objective To investigate whether there is an association between cholesterol-lowering medication use, specifically statins, and chronic polyneuropathy. Methods A literature study was carried out to assess the current state of evidence on the association between chronic polyneuropathy and cholesterol-lowering medication use. We also conducted a prospective case-control study to compare exposure to cholesterol-lowering medication between patients with cryptogenic axonal polyneuropathy and controls prior to the index date (defined in patients as date of onset of polyneuropathy symptoms, in controls as date of first study survey). Outcomes were adjusted for potential confounders such as cardiovascular history and metabolic syndrome. Results The 13 studies identified in our literature search showed conflicting results (odds ratios [ORs] ranging from 0.66 to 14.2), but most studies had methodologic limitations. There was insufficient evidence that statin use is a risk factor for polyneuropathy. Our prospective casecontrol study included 333 patients with cryptogenic axonal polyneuropathy and 283 controls. Patients with polyneuropathy were less likely to have been exposed to statins than controls (OR 0.56, 95% confidence interval 0.34-0.95, p = 0.03). The odds of polyneuropathy decreased as exposure duration to statins increased. Cholesterol-lowering medication consisted almost exclusively of statins; therefore we only draw conclusions on the effect of statin use. Conclusions Statin use does not increase the risk of chronic polyneuropathy. Therefore, statins should not be routinely withheld from polyneuropathy patients. Classification of evidence This study provides Class III evidence that statin use does not increase the risk of polyneuropathy. MORE ONLINE Class of Evidence Criteria for rating therapeutic and diagnostic studies NPub.org/coe From the UMC Utrecht Brain Center (J.

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Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Cited by 43 publications

References 36 publications

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

α- and β-Naphthoflavone synergistically attenuate H2O2-induced neuron SH-SY5Y cell damage

Statins do not increase risk of polyneuropathy

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