Oxidative Stress and Parkinson’s Disease: Effects on Environmental Toxicology

Epidemiological studies have found an increased risk of Parkinson’s disease (PD) with environmental factors such as exposure to substances derived from industrial processes, use of agrochemicals, or living in a rural environment. The hypothesis that certain environmental toxins could be the source of the EP is supported by the discovery that chemicals such as herbicides paraquat, diquat, and the fungicide maneb are selectively toxic in nigrostriatal dopaminergic neurons. Also, one of the insecticides produced by plants, such as rotenone, and by-product of the synthesis of synthetic heroin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can be reproduced in animal models where neurochemicals, histopathological, and clinical characteristic of PD can be found. Interestingly, there are similarities in the chemical structure of paraquat and MPTP. Recent evidence exhibited that inflammation and oxidative stress play an essential role in the development of PD. So, in our laboratory we found that in an animal model melatonin decreases the products of lipid oxidation, nitric oxide metabolites, and the activity of cyclooxygenase 2, which are induced by an intraperitoneal injection of MPTP. This suggests that the neuroprotective effects of melatonin are partially attributed to its antioxidant scavenging and anti-inflammatory action

Multiple Sclerosis and Its Relationship with Oxidative Stress, Glutathione Redox System, ATPase System, and Membrane Fluidity

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a focus on inflammation, demyelination, and damage to axons leading to neurological deficits. MS pathology is associated with excessive reactive oxygen species (ROS) and generation of reactive nitrogen species (RNS), causing oxidative/nitrosative stress. Deregulation of glutathione homeostasis and alterations in glutathione‐dependent enzymes are implicated in MS. Reactive oxygen species enhance both monocyte adhesion and migration across brain endothelial cells. In addition, ROS can activate the expression of the nuclear transcription factor‐kappa, which upregulates the expression of many genes involved in MS, such as tumor necrosis factor‐α and nitric oxide synthase, among others, leading to mitochondrial dysfunction and energy deficits that result in mitochondrial and cellular calcium overload. Loss of mitochondrial membrane potential can increase the release of cytochrome c, one pathway that leads to neuronal apoptosis. Clinical studies suggest that omega‐3 long‐chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti‐inflammatory, antioxidant, and neuroprotective effects in MS and animal models of MS. Here, we review the relationship of oxidative stress, the glutathione redox system, the ATPase system, and membrane fluidity with the development of MS. In addition, we describe the main findings of a clinical trial conducted with relapsing‐remitting MS patients who received a diet supplemented with 4 g/day of fish oil or olive oil. The effects of PUFAs supplementation on the parameters indicated above are analyzed in this work

Alzheimer’s Disease and SARS-CoV-2: Pathophysiological Analysis and Social Context

The COVID-19 pandemic has proven to be a challenge for healthcare systems, especially in terms of the care of patients with Alzheimer’s disease (AD). Age is one of the major risk factors for severe forms of COVID-19, most probably due to the presence of comorbidities and inflammations. It is known that SARS-CoV-2 invades nerve endings and olfactory nerves through the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction triggers an inflammatory cascade that results in cognitive impairment. In turn, the isoform of apolipoprotein-E4 (APOE-4ε) in AD is a risk factor for increased neuroinflammation through microglia activation, increased oxidative stress, and neurodegeneration. AD and SARS-CoV-2 are associated with increases in levels of inflammatory markers, as well as increases in levels of APOE-4ε, ACE2 and oxidative stress. Thus, there is a synergistic relationship between AD and SARS-CoV-2. In addition, the social isolation and other health measures resulting from the pandemic have led to a higher level of anxiety and depression among AD patients, a situation which may lead to a decline in cognitive function. Therefore, there is a need to develop strategies for keeping the patient calm but active

Prevalence of Cognitive Impairment and Depression among a Population Aged over 60 Years in the Metropolitan Area of Guadalajara, Mexico

Background. Cognitive impairment is an important clinical issue among elderly patients with depression and has a more complex etiology because of the variable rate of neurodegenerative changes associated with depression. The aim of the present work was to examine the prevalence of cognitive impairment and depression in a representative sample of adults aged ≥60 years. Methods. The presented work was a cross-sectional study on the prevalence of cognitive impairment and depression. Door-to-door interview technique was assigned in condition with multistage probability random sampling to obtain subjects that represent a population of the Guadalajara metropolitan area (GMA), Mexico. Cognitive function and depression were assessed by applying standardized Mini-Mental State Examination of Folstein (MMSE) and the Geriatric Depression Scale (GDS), respectively. Results. Prevalence of cognitive impairment was 13.8% (14.5% women, 12.6% men); no significant differences by gender and retired or pensioner were found. Prevalence of depression was 29.1% (33.6% women, 21.1% men); no significant differences by retired or pensioner were found. Cognitive impairment was associated with depression (OR  =  3.26, CI 95%, 2.31–4.60). Prevalence of cognitive impairment and depression is associated with: being woman, only in depression being older than 75 years being married, and a low level of education. Conclusion. Cognitive impairment and depression are highly correlated in adults aged ≥60

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

Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma.El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática