Publications by authors named "Fermín Pacheco-Moisés"

38 Publications

Occupational exposure to organophosphorus and carbamates in farmers in La Cienega, Jalisco, Mexico: oxidative stress and membrane fluidity markers.

J Occup Med Toxicol 2020 28;15:32. Epub 2020 Oct 28.

Department of Medical Sciences and Life, CUCIENEGA, University of Guadalajara, Ocotlan, Jalisco Mexico.

Background: The region of La Cienega in Jalisco Mexico, is an important agricultural reference for the production of corn, sorghum and wheat, among other grains, so the use of pesticides for pest control is high. However, in this rural area there are no toxicological studies that assess the occupational risk of pesticide use. Therefore, this study is the first to determine the oxidative stress levels markers (GSH, GSSG, carbonyl groups, nitric oxide metabolites and lipid peroxides) as well as alteration of the mitochondrial membrane fluidity caused by occupational exposure to organophosphorus and carbamates in farmers of this region. This occupational risk can increase cellular oxidation, which explains the high prevalence of neurodegenerative diseases and cancer in Cienega settlers to be analyzed in future studies.

Methods: Comparative cross-sectional study was performed using two groups: one not exposed group ( = 93) and another one with occupational exposure ( = 113). The latter group was sub-divided into 4 groups based on duration of use/exposure to pesticides. Oxidative stress levels and membrane fluidity were assessed using spectrophotometric methods. Statistical analyses were performed using SPSS software ver. 19.0 for windows.

Results: The most commonly used pesticides were organophosphorus, carbamates, herbicide-type glyphosate and paraquat, with an average occupational exposure time of 35.3 years. There were statistically significant differences in markers of oxidative stress between exposed farmers and not exposed group ( = 0.000). However, in most cases, no significant differences were found in markers of oxidative stress among the 4 exposure sub-groups ( > 0.05).

Conclusion: In the Cienega region, despite the indiscriminate use of organophosphorus and carbamates, there are no previous studies of levels oxidative stress. The results show increased levels of oxidative stress in occupationally exposed farmers, particularly membrane fluidity levels increased three times in contrast to not exposed group.
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http://dx.doi.org/10.1186/s12995-020-00283-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594453PMC
October 2020

Are electrophysiological and oligodendrocyte alterations an element in the development of multiple sclerosis at the same time as or before the immune response?

Int J Neurosci 2020 Jun 29:1-10. Epub 2020 Jun 29.

Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara, Mexico.

Efficient communication between the glial cells and neurons is a bi-directional process that is essential for conserving normal functioning in the central nervous system (CNS). Neurons dynamically regulate other brain cells in the healthy brain, yet little is known about the first pathways involving oligodendrocytes and neurons. Oligodendrocytes are the myelin-forming cells in the CNS that are needed for the propagation of action potentials along axons and additionally serve to support neurons by neurotrophic factors (NFTs). In demyelinating diseases, like multiple sclerosis (MS), oligodendrocytes are thought to be the victims. Axonal damage begins early and remains silent for years, and neurological disability develops when a threshold of axonal loss is reached, and the compensatory mechanisms are depleted. Three hypotheses have been proposed to explain axonal damage: 1) the damage is caused by an inflammatory process; 2) there is an excessive accumulation of intra-axonal calcium levels; and, 3) demyelinated axons evolve to a degenerative process resulting from the lack of trophic support provided by myelin or myelin-forming cells. Although MS was traditionally considered to be a white matter disease, the demyelination process also occurs in the cerebral cortex. Recent data supports the notion that initial response is triggered by CNS injury. Thus, the understanding of the role of neuron-glial neurophysiology would help provide us with further explanations. We should take in account the suggestion that MS is in part an autoimmune disease that involves genetic and environmental factors, and the pathological response leads to demyelination, axonal loss and inflammatory infiltrates.
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http://dx.doi.org/10.1080/00207454.2020.1786087DOI Listing
June 2020

Folate- and glucuronate-functionalization of layered double hydroxides containing dysprosium and gadolinium and the effect on oxidative stress in rat liver mitochondria.

Heliyon 2020 Jan 31;6(1):e03111. Epub 2019 Dec 31.

Departamento de Química, Universidad de Guadalajara, Marcelino García Barragán 1421, colonia Olímpica, C.P. 44430, Guadalajara, Jalisco, Mexico.

Zinc/aluminum layered double hydroxide (LDH) particles were prepared by alkaline precipitation in the presence of dysprosium and dysprosium/gadolinium cations. The particles formed were stable against exchange reactions with folate or glucuronate ions since these organic ions exclusively functionalized the external surface of the layered double hydroxides. While the dysprosium derivatives reached magnetization susceptibilities between 2.06 × 10 and 2.20 × 10 cm/g, the samples simultaneously containing dysprosium and gadolinium decreased to a range between 1.08 × 10 and 1.73 × 10 cm/g. This last sample was tested as a magnetic resonance imaging contrast agent and demonstrated a reduction in T1 and T2 relaxation times in a linear dependence with the LDH concentration. The oxidative stress assays in rat liver mitochondria demonstrated the low toxicity of the composition simultaneously containing dysprosium and gadolinium as well as the functionalization product with glucuronate ions, suggesting the potential of these particles to design alternative MRI contrast agents.
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http://dx.doi.org/10.1016/j.heliyon.2019.e03111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940671PMC
January 2020

The Role of Cardiolipin and Mitochondrial Damage in Kidney Transplant.

Oxid Med Cell Longev 2019 25;2019:3836186. Epub 2019 Nov 25.

Departamento de Química del Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Chronic kidney disease (CKD) is highly incident and prevalent in the world. The death of patients with CKD is primarily due to cardiovascular disease. Renal transplantation (RT) emerges as the best management alternative for patients with CKD. However, the incidence of acute renal graft dysfunction is 11.8% of the related living donor and 17.4% of the cadaveric donor. Anticardiolipin antibodies (ACAs) or antiphospholipid antibodies (APAs) are important risk factors for acute renal graft dysfunction. The determination of ACA or APA to candidates for RT could serve as prognostic markers of early graft failure and would indicate which patients could benefit from anticoagulant therapy. Cardiolipin is a fundamental molecule that plays an important role in the adequate conformation of the mitochondrial cristae and the correct assembly of the mitochondrial respiratory supercomplexes and other proteins essential for proper mitochondrial function. Cardiolipin undergoes a nonrandom oxidation process by having pronounced specificity unrelated to the polyunsaturation pattern of its acyl groups. Accumulation of hydroxyl derivatives and cardiolipin hydroperoxides has been observed in the affected tissues, and recent studies showed that oxidation of cardiolipin is carried out by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. Cardiolipin could be responsible for the proapoptotic production of death signals. Cardiolipin modulates the production of energy and participates in inflammation, mitophagy, and cellular apoptosis. The determination of cardiolipin or its antibodies is an attractive therapeutic, diagnostic target in RT and kidney diseases.
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http://dx.doi.org/10.1155/2019/3836186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899302PMC
May 2020

Heats of combustion of the main carbohydrates contained in plant-source foods.

Nutr Rev 2020 05;78(5):382-393

Chemistry Department, University Center of Exact Sciences and Engineering, University of Guadalajara, Guadalajara, Jalisco, Mexico.

In a previous review, the experiments of American chemist W.O. Atwater were critically examined, with the findings demonstrating certain weaknesses that could compromise the validity of the values currently used for metabolizable energy. An examination of published works on the heat of combustion of carbohydrates reveals 2 types of weaknesses: the inaccuracy and imprecision of the calorimetric data used, and the averaging procedure employed to estimate such representative values. The present review focuses on the first type of weakness, namely the inaccuracy and imprecision of the calorimetric data used in previous studies. An exhaustive bibliographic search yielded almost 100 heat of combustion values for some of the 6 main carbohydrates contained in plant-source foods (glucose, fructose, sucrose, maltose, starch, and cellulose). These heats of combustion were subjected to rigorous statistical analysis to propose the following for each carbohydrate: (1) an interval (termed a bibliographic interval) that very likely includes the actual heat of combustion value and (2) a "representative value" (calculated to produce the minimum level of inaccuracy). In addition, an estimation of the maximum level of inaccuracy that could be expected when using such a representative value is reported.
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http://dx.doi.org/10.1093/nutrit/nuz063DOI Listing
May 2020

Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis.

Arch Med Res 2018 08 27;49(6):391-398. Epub 2018 Dec 27.

Laboratorio de Desarrollo, Envejecimiento y Enfermedades Neurodegenerativas, División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system (CNS). Neuroinflammation and oxidative stress are involved in the pathogenesis of MS, promoting tissue damage and demielinization. Current research findings suggest that melatonin has antioxidant and neuroprotective effects. The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis (RRMS). 36 patients diagnose with RRMS treated with Interferon β-1b (IFNβ-1b) were enrolled in a double bind, randomized, placebo controlled trial. The experimental group received orally 25 mg/d of melatonin for 6 months. After melatonin administration, we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers; 18% for TNF-α (p <0.05), 34.8% for IL-1β (p <0.05), 34.7% for IL-6 (p <0.05), 39.9% for lipoperoxides (LPO) (p <0.05) and 24% for nitric oxide catabolites (NOC) levels (p <0.05), compared with placebo group. No significant difference in clinical efficacy outcomes were found between groups. Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups. We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS. These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients.
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http://dx.doi.org/10.1016/j.arcmed.2018.12.004DOI Listing
August 2018

Effect of symbiotic supplementation on fecal calprotectin levels and lactic acid bacteria, Bifidobacteria, Escherichia coli and Salmonella DNA in patients with cervical cancer.

Nutr Hosp 2018 Dec 3;35(6):1394-1400. Epub 2018 Dec 3.

Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS).

Background: patients with cervical cancer (CC) receiving chemotherapy and radiotherapy have several gastrointestinal adverse effects.

Objective: to evaluate the effect of dietary symbiotic supplementation on fecal calprotectin (FCP), bacterial DNA levels, and gastrointestinal adverse effects in patients with CC.

Methods: clinical, controlled, randomized, double-blind trial. Patients consumed symbiotics or placebo three times a day for seven weeks. FCP was assessed by Elisa method. DNA from probiotic and pathogenic bacteria were determined by quantitative real-time polymerase chain reaction. Diarrheal evacuations were evaluated with the Bristol stool form scale and nausea and vomiting were measured using the scale of the National Institute of Cancerology of the United States.

Results: after a seven-week treatment, FCP concentration was lower in the symbiotic group compared to the control group (p < 0.001). Stool consistency in the placebo and symbiotic groups was similar at baseline. A significant improvement in stool consistency was obtained in both groups at the end of the intervention (p < 0.001). The concentrations and total proportions of the probiotic and pathogenic bacteria were similar in both groups. Nausea significantly diminished in both groups (p < 0.001) at the end of the trial. Furthermore, the symbiotic group had a statistically significant decrease in the frequency and intensity of vomiting when compared to the control group (p < 0.001).

Conclusions: the symbiotic treatment decreases significantly the FCP levels and the frequency and intensity of vomiting in patients with CC.
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http://dx.doi.org/10.20960/nh.1762DOI Listing
December 2018

Two-Dimensional Thin Layer Chromatography-Bioautography Designed to Separate and Locate Metabolites with Antioxidant Activity Contained on .

Int J Anal Chem 2018 5;2018:4605373. Epub 2018 Jul 5.

Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán 1421, 44430 Guadalajara, Jalisco, Mexico.

contains several biologically active compounds, some of them with antioxidant activity. Nevertheless, not all of these compounds have been identified to date. As a first step to achieving such identification, a methodology to perform two-dimensional thin layer chromatography bioautographies on silica gel thin layer chromatography plates was proposed. Starting with a reference binary system, 5 other binary systems were tested, in which the relative polarity was systematically increased. To further improve the separation behavior, a phase modifier (NHOH) was used. The best separation results were obtained with the isopropyl alcohol/ethyl acetate/NHOH ternary system. This experimental system allowed four well-resolved spots showing antioxidant activity as well as two additional areas with mixtures containing antioxidant compounds. Although the proposed methodology was designed with a specific application, it would be predictable that its field of use could be considerably greater, making the convenient modifications on the solvent polarity and "masking level" produced by the ammonium derivatives.
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http://dx.doi.org/10.1155/2018/4605373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077365PMC
July 2018

Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b.

Nutr Hosp 2018 Jan 12;35(1):162-168. Epub 2018 Jan 12.

.

Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS).

Objective: To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement.

Methods: Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified.

Results: In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized.

Conclusion: The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.
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http://dx.doi.org/10.20960/nh.1084DOI Listing
January 2018

The Role of Oxidative Stress, Mitochondrial Function, and Autophagy in Diabetic Polyneuropathy.

J Diabetes Res 2017 24;2017:1673081. Epub 2017 Oct 24.

Institute of Experimental and Clinical Therapeutics, Department of Physiology, University Health Sciences Centre, University of Guadalajara, Guadalajara, JAL, Mexico.

Diabetic polyneuropathy (DPN) is the most frequent and prevalent chronic complication of diabetes mellitus (DM). The state of persistent hyperglycemia leads to an increase in the production of cytosolic and mitochondrial reactive oxygen species (ROS) and favors deregulation of the antioxidant defenses that are capable of activating diverse metabolic pathways which trigger the presence of nitro-oxidative stress (NOS) and endoplasmic reticulum stress. Hyperglycemia provokes the appearance of micro- and macrovascular complications and favors oxidative damage to the macromolecules (lipids, carbohydrates, and proteins) with an increase in products that damage the DNA. Hyperglycemia produces mitochondrial dysfunction with deregulation between mitochondrial fission/fusion and regulatory factors. Mitochondrial fission appears early in diabetic neuropathy with the ability to facilitate mitochondrial fragmentation. Autophagy is a catabolic process induced by oxidative stress that involves the formation of vesicles by the lysosomes. Autophagy protects cells from diverse stress factors and routine deterioration. Clarification of the mechanisms involved in the appearance of complications in DM will facilitate the selection of specific therapeutic options based on the mechanisms involved in the metabolic pathways affected. Nowadays, the antioxidant agents consumed exogenously form an adjuvant therapeutic alternative in chronic degenerative metabolic diseases, such as DM.
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http://dx.doi.org/10.1155/2017/1673081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674726PMC
July 2018

Oxidative Stress: Love and Hate History in Central Nervous System.

Adv Protein Chem Struct Biol 2017 7;108:1-31. Epub 2017 Mar 7.

Laboratorio de Mitocondria-Estrés Oxidativo y Patología, División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.

Molecular oxygen is essential for aerobic organisms in order to synthesize large amounts of energy during the process of oxidative phosphorylation and it is harnessed in the form of adenosine triphosphate, the chemical energy of the cell. Oxygen is toxic for anaerobic organisms but it is also less obvious that oxygen is poisonous to aerobic organisms at higher concentrations of oxygen. For instance, oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at increased partial pressures. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen that are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, in pathological conditions ROS levels can increase dramatically. This may result in significant damage to cell structures. Living organisms have been adapted to the ROS in two ways: they can mitigate the unwanted effects through removal by the antioxidant systems and can advantageously use them as messengers in cell signaling and regulation of body functions. Some other physiological functions of ROS include the regulation of vascular tone, detection, and adaptation to hypoxia. In this review, we describe the mechanisms of oxidative damage and its relationship with the most highly studied neurodegenerative diseases.
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http://dx.doi.org/10.1016/bs.apcsb.2017.01.003DOI Listing
October 2017

Effect of fish oil on glutathione redox system in multiple sclerosis.

Am J Neurodegener Dis 2016 1;5(2):145-51. Epub 2016 Jun 1.

OPD Instituto Jalisciense de Cancerología SSA-Jalisco. Guadalajara, Jalisco. México.

Unlabelled: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system. Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are implicated in the induction and progression of MS. Evidence suggests that Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory, antioxidant and neuroprotective effects. The aim of the present work was to evaluate the effect of fish oil on the activity of glutathione reductase (GR), content of reduced and oxidized glutathione, and GSH/GSSG ratio in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. Fish oil supplementation resulted in a significant increase in n-3 fatty acids and a decrease n-6 fatty acids. No differences in glutathione reductase activity, content of reduced and oxidized glutathione, and GSH/GSSG ratio were found.

Conclusion: Glutathione reductase activity was not significantly different between the groups; however, fish oil supplementation resulted in smaller increase in GR compared with control group, suggesting a possible effect on antioxidant defence mechanisms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913222PMC
June 2016

Omega 3 Fatty Acids Supplementation and Oxidative Stress in HIV-Seropositive Patients. A Clinical Trial.

PLoS One 2016 25;11(3):e0151637. Epub 2016 Mar 25.

Laboratory of oxidative stress & Pathology, Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Mexico.

HIV-seropositive patients show high incidence of coronary heart disease and oxidative stress has been described as relevant key in atherosclerosis development. The aim of this study was to assess the effect of omega 3 fatty acids on different markers of oxidative stress in HIV-seropositive patients. We performed a randomized parallel controlled clinical trial in The Instituto Mexicano del Seguro Social, a public health hospital. 70 HIV-seropositive patients aged 20 to 55 on clinical score A1, A2, B1 or B2 receiving highly active antiretroviral therapy (HAART) were studied. They were randomly assigned to receive omega 3 fatty acids 2.4 g (Zonelabs, Marblehead MA) or placebo for 6 months. At baseline and at the end of the study, anthropometric measurements, lipid profile, glucose and stress oxidative levels [nitric oxide catabolites, lipoperoxides (malondialdehyde plus 4-hydroxialkenals), and glutathione] were evaluated. Principal HAART therapy was EFV/TDF/FTC (55%) and AZT/3TC/EFV (15%) without difference between groups. Treatment with omega 3 fatty acids as compared with placebo decreased triglycerides (-0.32 vs. 0.54 mmol/L; p = 0.04), but oxidative stress markers were not different between groups.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151637PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807787PMC
August 2016

[NUTRITIONAL AND SOCIODEMOGRAPHIC FACTORS IN PARKINSON'S DISEASE: RURAL VIEW].

Nutr Hosp 2015 Dec 1;32(6):2783-91. Epub 2015 Dec 1.

Departamento de Química. Centro Universitario de Ciencias Exactas e Ingenierías. Universidad de Guadalajara, Guadalajara, Jalisco..

Parkinson's disease (PD), its prevalent in population to 65 years of age, nevertheless can occur earlier. Patients with PD exhibit motor and no motor symptoms these may relate with changes in nutritional habits during disease progression. The prevalence of PD and nutritional factor could be different in rural areas compared to urban regions and can be associated with sociocultural and demographic features. It has been suggested a possible association between excessive intake of saturated fats and low consumption of vitamins such as B6 with EP, however, the results are still not conclusive. Some of significant factors could affect nutritional habits and status in PD in rural areas, are: health status, economic availability, environmental and geographical factors, among others. This review presents some eating habits and sociodemographic factors in PD principally in rural areas.
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http://dx.doi.org/10.3305/nh.2015.32.6.9742DOI Listing
December 2015

Thrombin generation and international normalized ratio in inherited thrombophilia patients receiving thromboprophylactic therapy.

Thromb Res 2015 Dec 19;136(6):1291-8. Epub 2015 Oct 19.

División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México. Electronic address:

Background: Thrombin generation assay (TGA) is useful as a global functional test for assessing bleeding or thrombotic risk and its modification with therapy. We investigated TGA to assess anticoagulation status compared with the international normalized ratio (INR) system in patients with primary thrombophilia receiving and not undergoing thromboprophylaxis.

Materials And Methods: We studied 50 patients with at least one thrombotic event and a confirmed diagnosis of inherited thrombophilia. Thrombin generation was measured in platelet-poor plasma by calibrated automated thrombography (CAT).

Results: Patients in optimal anticoagulation (INR: 2.0-3.0) showed an endogenous thrombin potential (ETP) of 14-56% of normal and a peak of 18-55% of normal. A significant inverse relationship between INR and thrombin generation parameters (ETP, peak and velocity index) and a linear correlation for lag time was found in patients treated with vitamin-K antagonists (VKA). Receiver-operating characteristics (ROC) analysis showed that the optimal cutoff for ETP was 1600.2 nM · min (111.6% of normal, with a sensitivity of 96.6% and a specificity of 92.9%) and for the peak was 298.3 nM (112.1% of normal, with a sensitivity of 96.4% and a specificity of 100%). According to this analysis, ETP was able to identify patients with increased thrombotic and hemorrhagic risk, correlating with severe clinical complications.

Conclusion: TGA showed excellent sensitivity and specificity for assessing anticoagulation status in patients with primary thrombophilia receiving VKA, with significant advantages with regard to INR. Clinical data strongly support ETP as a valuable indicator of thrombotic or hemorrhagic risk in patients receiving or not receiving thromboprophylaxis.
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http://dx.doi.org/10.1016/j.thromres.2015.10.026DOI Listing
December 2015

The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

Redox Rep 2016 Jul 31;21(4):155-63. Epub 2015 Aug 31.

a Department of Physiology , Clinical and Experimental Treatment Institute, University Health Sciences Centre, University of Guadalajara,  Mexico (Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología).

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.
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http://dx.doi.org/10.1179/1351000215Y.0000000040DOI Listing
July 2016

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

Oxid Med Cell Longev 2015 28;2015:756294. Epub 2015 Jul 28.

Instituto de Terapéutica Experimental y Clínica, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, JAL, Mexico.

Objective: To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN).

Methods: We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis.

Results: LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores.

Discussion: EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.
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http://dx.doi.org/10.1155/2015/756294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531178PMC
May 2016

The antioxidant effect of ubiquinone and combined therapy on mitochondrial function in blood cells in non-proliferative diabetic retinopathy: A randomized, double-blind, phase IIa, placebo-controlled study.

Redox Rep 2016 Jul 5;21(4):190-5. Epub 2016 Feb 5.

a University Health Sciences Center, University of Guadalajara (Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara) , Guadalajara , Jalisco , México.

Objectives: To evaluate the effect of ubiquinone and combined antioxidant therapy on mitochondrial function in non-proliferative diabetic retinopathy (NPDR) in a randomized, double-blind, phase IIa, placebo-controlled, clinical trial. Three groups of 20 patients were formed: Group 1, ubiquinone; Group 2, combined therapy; and Group 3, placebo (one daily dose for 6 months).

Methods: Fluidity of the submitochondrial membrane in platelets was determined by examining intensity of fluorescence between the monomer (Im) and excimer (Ie). Hydrolytic activity of the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method.

Results: Normal, baseline submitochondrial membrane fluidity, 0.24 ± 0.01 Ie/Im, was significantly diminished in the three study groups vs. normal values (P < 0.0001); placebo, 0.14 ± 0.01 Ie/Im; ubiquinone, 0.14 ± 0.01 Ie/Im; and combined therapy, 0.13 ± 0.00 Ie/Im. Afterward, it increased significantly (P < 0.0001), the ubiquinone group 0.22 ± 0.01 Ie/Im, combined therapy group, 0.19 ± 0.01 Ie/Im; with no changes the placebo group. Baseline hydrolytic activity of the F0F1-ATPase enzyme increased in the three study groups vs. normal values (184.50 ± 7.84 nmol PO4), placebo, 304.12 ± 22.83 nmol PO4 (P < 0.002); ubiquinone, 312.41 ± 25.63 nmol PO4 (P < 0.009); and combined therapy, 371.28 ± 33.50 nmol PO4 (P < 0.002). Afterward, a significant decrease the enzymatic activity: ubiquinone, 213.25 ± 14.19 nmol PO4 (P < 0.001); and combined therapy, 225.55 ± 14.48 nmol PO4 (P < 0.0001).

Discussion: Mitochondrial dysfunction significantly improved in groups of NPDR patients treated with antioxidants.
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http://dx.doi.org/10.1179/1351000215Y.0000000032DOI Listing
July 2016

Mitochondrial ATPase activity and membrane fluidity changes in rat liver in response to intoxication with buckthorn (Karwinskia humboldtiana).

Biol Res 2015 Mar 19;48:17. Epub 2015 Mar 19.

Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán 1421, 44430, Guadalajara, Jalisco, Mexico.

Background: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1, 1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment.

Results: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase.

Conclusions: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.
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http://dx.doi.org/10.1186/s40659-015-0008-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376499PMC
March 2015

Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction after functionalization with folic and glucuronic acids.

Mater Sci Eng C Mater Biol Appl 2015 Mar 10;48:541-7. Epub 2014 Dec 10.

Departamento de Química, Universidad de Guadalajara, Marcelino García Barragán 1421, C.P. 44430, Guadalajara, Jalisco, Mexico. Electronic address:

The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity.
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http://dx.doi.org/10.1016/j.msec.2014.12.033DOI Listing
March 2015

Beneficial effects of quercetin on oxidative stress in liver and kidney induced by titanium dioxide (TiO2) nanoparticles in rats.

Toxicol Mech Methods 2015 Mar 11;25(3):166-75. Epub 2015 Feb 11.

Doctorado en Farmacología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara (UDG) , Guadalajara, Jalisco , México .

TiO2 nanoparticles used as vectors for the delivery of drugs have shown greater effectiveness. However, TiO2 nanoparticles can cause oxidative stress in liver and kidney, so we analyzed if a previous or simultaneous quercetin treatment could counteract this in rats. Five groups of male Wistar rats (200-250 g) were included: (1) healthy controls, (2) TiO2 group, (3) quercetin group, (4) preventive group: quercetin for 5 days prior to exposure of TiO2, and (5) therapeutic group: TiO2 (5 mg/kg, i.v.) plus quercetin single dose for 5 days (5 mg/kg/day, i.p.). Hepatic and renal function tests were made. Five animals from each group were sacrificed (0, 14 and 28 days), and liver and kidney tissue were obtained. Malondialdehyde (MDA), reduced/oxidized glutathione, and activity of glutathione peroxidase/reductase were measured, as well as the level of gene expression by q-PCR. There were no significant changes in serum ALT and AST activities. More damage was observed at 14 versus 28 days, because TiO2 was excreted in urine. Quercetin indeed showed a renal protective effect by increasing glutathione reductase and peroxidase levels and reducing MDA levels. On the other hand, TiO2 liver damage was less pronounced with quercetin as therapeutic treatment. TiO2 induces significantly the glutathione reductase expression and it can be down-regulated by quercetin. Biochemical tests in serum and urine showed a better effect of quercetin administered in the therapeutic group. Care should be taken with the dose and time of administration of quercetin, because this antioxidant could also have a pro-oxidant effect.
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http://dx.doi.org/10.3109/15376516.2015.1006491DOI Listing
March 2015

[Levels of oxidative stress in serum and dietary behavior in adults in a rural area of Jalisco, Mexico].

Nutr Hosp 2014 Dec 1;31(1):341-50. Epub 2014 Dec 1.

División de Neurosciencias, Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Jalisco..

Introduction: The feeding behavior establishes a relation of humans with food, includes food habits that could be involved with oxidative stress.

Objective: To evaluate the relation of indicators of oxidative stress (lipid peroxides) and antioxidant (ascorbic acid, catalase, superoxide dismutase) with feeding behavior in adults of Teocuhitatlan Corona, Jalisco, Mexico.

Method: Study observational, descriptive, cross-sectional of 44 adults with 43 to 88 years, was used a instrument of feeding behavior. The questionnaire were related to indicators of oxidative stress. Were used descriptive statistics, frequency distribution and analysis of covariance with adjustment variables, was considered significant p <0.05.

Results: The values of serum lipid peroxides were related to behaviors: consider the nutritional content as most important when choosing food (p = 0.042), dislike milk (p = 0.027), intake of sweets between meals (p = 0.001), habitual inclusion of vegetables and salads in main meal (p = 0.018). We do not found association in to values of ascorbic acid, cholesterol in low density lipoproteins and enzymatic activities of catalase and superoxide dismutase with food behaviors.

Discussion: The feeding behaviors analyzed in this study may be involved with development of oxidative stress and could be have protective or harmful effect in development to complications of chronic non-communicable diseases and aging in this population. This suggests to analyze demographic and socio-cultural aspects of region and besides analyzing the consumption and metabolic markers related to food.
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http://dx.doi.org/10.3305/nh.2015.31.1.7824DOI Listing
December 2014

Effect of necrosectomy and vacuum-assisted closure (VAC) on mitochondrial function and oxidative stress markers in severe acute pancreatitis.

Rev Esp Enferm Dig 2014 Dec;106(8):505-14

Background: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality.

Objective: To evaluate whether necrosectomy, alone or combined with vacuum-assisted closure (VAC), has any additional beneficial effects on mitochondrial function and/or oxidative stress markers in SAP.

Methods: Patients with SAP, APACHE II score > 8, and inadequate response to management in an intensive care unit were included in a prospective observational study. Sixteen underwent necrosectomy and 24 underwent necrosectomy plus VAC every 48 h. Patients were then categorized as survivors or deceased. Submitochondrial membrane fluidity of platelets and F0F1-ATPase hydrolysis were measured to represent mitochondrial function. Oxidative/nitrosative stress was measured using lipoperoxides (LPOs), nitric oxide (NO), erythrocyte membrane fluidity, and total antioxidant capacity (TAC).

Results: Membrane fluidity in submitochondrial particles of platelets remained significantly increased throughout the study, and then eventually rised in deceased patients managed with necrosectomy + VAC vs. survivors (p < 0.041). Hydrolysis was significantly increased from baseline to endpoint in all patients, predominating in those who died after management with necrosectomy (p < 0.03). LPO increased in all patients, and necrosectomy was more efficient for the eventual decrease in survivors (p < 0.039). NO was found to be increased for the baseline-endpoint result among both survivors and deceased patients with both management options. Erythrocyte membrane fluidity was increased in survivors managed with necrosectomy + VAC, and eventually returned to normal (p < 0.045). TAC was found to be consumed in all patients for the duration of the study.

Conclusions: Mitochondrial dysfunction and oxidative/ nitrosative stress with significant systemic antioxidant consumption were found. Necrosectomy was more efficient and better cleared LPOs. Necrosectomy + VAC improved erythrocyte membrane fluidity and increased survival.
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December 2014

Role of the blood-brain barrier in multiple sclerosis.

Arch Med Res 2014 Nov 26;45(8):687-97. Epub 2014 Nov 26.

Laboratorio Desarrollo-Envejecimiento, Enfermedades Neurodegenerativas, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients.
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http://dx.doi.org/10.1016/j.arcmed.2014.11.013DOI Listing
November 2014

Prevalence of Dementia, Emotional State and Physical Performance among Older Adults in the Metropolitan Area of Guadalajara, Jalisco, Mexico.

Curr Gerontol Geriatr Res 2014 27;2014:387528. Epub 2014 Mar 27.

Departamento de Neurología, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional de Occidente (CMNO), IMSS, Belisario Domínguez 1000, 44340, Guadalajara, JAL, Mexico.

Background. Dementia affects memory, thinking, language, judgment, and behavior. Depression, is common in older adults with dementia. The concomitance of dementia and depression increases disability with impaired activities of daily living (ADL), increasing the chances of institutionalization and mortality. Methods. Cross-sectional study of a population 60 years and older who live in the State of Jalisco, Mexico. A total of 1142 persons were assessed regarding their cognitive function, emotional state, and physical performance. Door-to-door interview technique was assigned in condition with multistage probability random sampling. Cognitive function, depression and functional disability were assessed by applying standardized Minimental State Examination (Folstein), Geriatric Depression Scale, and the Katz index, respectively. Diagnosis of dementia was performed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, the Fourth Edition. Data were analyzed using SPSS software. Results. Prevalence of demency was 9.5% (63.35% women, and 36.7% men). Demency was associated with being woman, being older than 70 years, low level of education, not having the economic benefit of retirement, being single or living without a partner, low level of education, suffering from depression and have functional disability in ADL. Conclusion. Dementia is more common in women and is related to depression and disability.
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http://dx.doi.org/10.1155/2014/387528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985183PMC
May 2014

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease.

Int J Alzheimers Dis 2014 18;2014:794530. Epub 2014 Feb 18.

Laboratorio de Desarrollo-Envejecimiento: Enfermedades Neurodegenerativas, División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada No. 800 colonia Independencia 44340 Guadalajara, JAL, Mexico.

Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.
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http://dx.doi.org/10.1155/2014/794530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950951PMC
April 2014

Dietary fat and antioxidant vitamin intake in patients of neurodegenerative disease in a rural region of Jalisco, Mexico.

Nutr Neurosci 2014 Nov 20;17(6):260-7. Epub 2013 Nov 20.

Objective: To evaluate and compare the intake of lipids and (A, E, and C) vitamins in patients with and without possible neurodegenerative diseases.

Methods: Twenty adults with possible Alzheimer's disease or Parkinson's disease and 41 control subjects (50-89 years old) from a rural region were studied. Dietary intake was evaluated with the analysis of macronutrients and micronutrients conducted by a food frequency questionnaire and 24 hours dietary record. Analyses were adjusted for age, sex, body mass index, and energy intake. Through interrogation and use of medical record form of health secretary we obtained information about the sociodemographic characteristics. Multivariate analysis of variance to allow for covariated adjustment was used.

Results: Patients had a lower energy intake, vitamin C (P = 0.016), fruits (P < 0.001), vegetables (P = 0.037), and oils and fat (P = 0.002), than the controls. Interestingly, the C vitamin intake in patients was still higher than the recommended. Patients had a higher consumption of cereals (P = 0.017), high-animal fat diet (P = 0.024), and whole milk (P < 0.001); 2.4% of the controls smoke and 5% are alcohol consumers. Eighty-five percent of patients and 78% of the controls do not have physical activity. Family history of subjects in this study indicated chronic diseases.

Conclusion: The subjects included in this study had a high intake of C vitamin, this is due to the consumption of fruits and vegetables. However, patients with possible Alzheimer's or Parkinson's disease had a lower intake of fruits and vegetables, which could be due to type of food to which they have access.
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http://dx.doi.org/10.1179/1476830513Y.0000000089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172311PMC
November 2014

Immunology and oxidative stress in multiple sclerosis: clinical and basic approach.

Clin Dev Immunol 2013 24;2013:708659. Epub 2013 Sep 24.

Laboratorio de Mitocondria-Estrés Oxidativo y Patología, División de Neurociencias, Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Sierra Mojada 800, CP 44340 Guadalajara, Jalisco, Mexico.

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.
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http://dx.doi.org/10.1155/2013/708659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794553PMC
June 2014

Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic retinopathy.

J Diabetes 2014 Mar 21;6(2):167-75. Epub 2013 Aug 21.

University Health Sciences Centre, University of Guadalajara, Guadalajara, México.

Background: Diabetic retinopathy (DR) is a preventable cause of visual disability. The aims of the present study were to investigate levels and behavior oxidative stress markers and mitochondrial function in non-proliferative DR (NPDR) and to establish the correlation between the severity of NPDR and markers of oxidative stress and mitochondrial function.

Methods: In a transverse analysis, type 2 diabetes mellitus (T2DM) patients with mild, moderate and severe non-proliferative DR (NPDR) were evaluated for markers of oxidative stress (i.e. products of lipid peroxidation (LPO) and nitric oxide (NO) catabolites) and antioxidant activity (i.e. total antioxidant capacity (TAC), catalase, and glutathione peroxidase (GPx) activity of erythrocytes). Mitochondrial function was also determined as the fluidity of the submitochondrial particles of platelets and the hydrolytic activity of F0 /F1 -ATPase.

Results: Levels of LPO and NO were significantly increased in T2DM patients with severe NPDR (3.19 ± 0.05 μmol/mL and 45.62 ± 1.27 pmol/mL, respectively; P < 0.007 and P < 0.0001 vs levels in health volunteers, respectively), suggesting the presence of oxidative stress. TAC had significant decrease levels with minimum peak in severe retinopathy with 7.98 ± 0.48 mEq/mL (P < 0.0001). In contrast with TAC, erythrocyte catalase and GPx activity was increased in patients with severe NPDR (139.4 ± 4.4 and 117.13 ± 14.84 U/mg, respectively; P < 0.0001 vs healthy volunteers for both), suggesting an imbalance between oxidants and antioxidants. The fluidity of membrane submitochondrial particles decreased significantly in T2DM patients with mild, moderate, or severe NPDR compared with that in healthy volunteers (P < 0.0001 for all). Furthermore, there was a significant increase in the hydrolytic activity of the F0 /F1 -ATPase in T2DM patients with mild NPDR (265.07 ± 29.55 nmol/PO4 ; P < 0.0001 vs healthy volunteers), suggesting increased catabolism.

Conclusions: Patients with NPDR exhibit oxidative deregulation with decreased membrane fluidity of submitochondrial particles and increased systemic catabolism (mitochondrial dysfunction) with the potential for generalized systemic damage in T2DM.
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http://dx.doi.org/10.1111/1753-0407.12076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232896PMC
March 2014

Fish oil, melatonin and vitamin E attenuates midbrain cyclooxygenase-2 activity and oxidative stress after the administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine.

Metab Brain Dis 2013 Dec 24;28(4):705-9. Epub 2013 May 24.

Laboratorio de Mitocondria-Estrés Oxidativo & Patología, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.

Parkinson's disease is a neurodegenerative disease whose hallmark pathological features include a selective loss of dopaminergic neurons in the midbrain. Ciclooxygenase-2 activity induction and oxidative stress have been implicated in the aetiology of Parkinson's disease and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Upon administration of fish oil, melatonin and vitamin E, neuroprotective effects on MPTP-induced neurotoxicity have been indicated. The aim of this study was to investigate the time course and compare the potency of these agents alone, on several parameters such as COX-2 and lipid peroxides (LPO) products associated with MPTP neurotoxicity in midbrain homogenates of C57BL/6 mice. Using fish oil (0.0368 g EPA and 0.0184 g DHA, per day), melatonin (10 mg/kg/day), and vitamin E (50 mg/Kg/day) we have now shown that COX-2 activity, LPO and nitrite/nitrate levels were significantly increased in MPTP treated mice (p < 0.001) while fish oil, melatonin and vitamin E treatment were capable of decreasing significantly the outcome of all above noted parameters (p < 0.05). The effect of fish oil on COX-2 activity and nitrite/nitrate levels was more profound than that of vitamin E or melatonin while the latter was more effective on reducing the LPO levels compared to fish oil and vitamin E. In conclusion, the outcome of the neuroprotective effects of these agents is long lasting and of variable potency indicating a different anti-inflammatory mode of action.
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http://dx.doi.org/10.1007/s11011-013-9416-0DOI Listing
December 2013