The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At the moment, no effective treatments are available in the market, making the whole situation a compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to explain the etiology of this disease leading to the new concept that AD is a multifactor pathology. Among others, the function of mitochondria has been considered as one of the intracellular processes severely compromised in AD since the early stages and likely represents a common feature of many neurodegenerative diseases. Many mitochondrial parameters decline already during the aging, reaching an extensive functional failure concomitant with the onset of neurodegenerative conditions, although the exact timeline of these events is still unclear. Thereby, it is not surprising that mitochondria have been already considered as therapeutic targets in neurodegenerative diseases including AD. Together with an overview of the role of mitochondrial dysfunction, this review examines the pros and cons of the tested therapeutic approaches targeting mitochondria in the context of AD. Since mitochondrial therapies in AD have shown different degrees of progress, it is imperative to perform a detailed analysis of the significance of mitochondrial deterioration in AD and of a pharmacological treatment at this level. This step would be very important for the field, as an effective drug treatment in AD is still missing and new therapeutic concepts are urgently needed.

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Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update.

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

Activation of Nrf2 signaling by sitagliptin and quercetin combination against β‐amyloid induced Alzheimer's disease in rats

Background: The purpose of this review was to evaluate whether acute exercise intensities have unique effects on memory function, and whether this is influenced by memory type as well as the temporality of the acute exercise bout.Methods: A systematic review was employed, using several databases (PubMed, PsychInfo,Sports Discus, Google Scholar, Embase).Results: In total, 9 articles met the study criteria. All 9 studies evaluated either working memory capacity or episodic-related memory function. The main findings across these studies were 1) when acute exercise occurs before the memory task, high-intensity exercise may be less favorable for working memory but may favor episodic memory; 2) when acute exercise occurs during the memory task, high-intensity exercise may be less favorable for working memory capacity; and 3) high-intensity exercise may not associate with long-term memory function when it occurs shortly after memory encoding.Conclusion: The relationship between acute exercise and memory is complex and may vary based on the intensity of exercise, the temporality of exercise, and the memory type evaluated.

https://hpp.tbzmed.ac.ir/PDF/hpp-8-255.pdf

Intensity-specific effects of acute exercise on human memory function: considerations for the timing of exercise and the type of memory.

Significance: Epidemiological studies indicate that metabolic disorders are associated with an increased risk for Alzheimer's disease (AD). Metabolic remodeling occurs in the central nervous system...

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Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention

Alzheimer’s disease (AD) is the main aging-associated neurodegenerative disorder and is characterized by mitochondrial dysfunction, oxidative stress, synaptic failure, and cognitive decline. It has been a challenge to find disease course-modifying treatments. However, several studies demonstrated that regular physical activity and exercise are capable of promoting brain health by improving the cognitive function. Maternal lifestyle, including regular exercise during pregnancy, has also been shown to influence fetal development and disease susceptibility in adulthood through fetal metabolism programming. Here, we investigated the potential neuroprotective role of regular maternal swimming, before and during pregnancy, against amyloid-β neurotoxicity in the adult offspring. Behavioral and neurochemical analyses were performed 14 days after male offspring received a single, bilateral, intracerebroventricular (icv) injection of amyloid-β oligomers (AβOs). AβOs-injected rats of the sedentary maternal group exhibited learning and memory deficits, along with reduced synaptophysin, brain-derived neurotrophic factor (BDNF) levels, and alterations of mitochondrial function. Strikingly, the offspring of the sedentary maternal group had AβOs-induced behavioral alterations that were prevented by maternal exercise. This effect was accompanied by preventing the alteration of synaptophysin levels in the offspring of exercised dams. Additionally, offspring of the maternal exercise group exhibited an augmentation of functional mitochondria, as indicated by increases in mitochondrial mass and membrane potential, α-ketoglutarate dehydrogenase, and cytochrome c oxidase enzymes activities. Moreover, maternal exercise during pregnancy induced long-lasting modulation of fusion and fission proteins, Mfn1 and Drp1, respectively. Overall, our data demonstrates a potential protective effect of exercise during pregnancy against AβOs-induced neurotoxicity in the adult offspring brain, by mitigating the neurodegenerative process triggered by Alzheimer-associated AβOs through programming the brain metabolism.

Physical Exercise During Pregnancy Prevents Cognitive Impairment Induced by Amyloid-β in Adult Offspring Rats

Dietary restriction increases life span and protects distinct organisms against a series of diseases, among which, those related to oxidative stress, like neurodegenerative diseases. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. We aimed to assess the effects of 40% food restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, and oxidative damage parameters in the cerebellum and total cerebral cortex of pregnant rats and their offspring. Dams and pups showed oxidative modulation caused by food restriction in both structures. Dichlorofluorescein oxidation, reflecting reactive species levels, was reduced in the cerebellum of dams and offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in the cortex. We also measured the activities of important antioxidant enzymes responsible by reactive oxygen species elimination. Superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased in dams' cerebral cortex. Both brain structures were affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were reduced in pups and dams. Non-enzymatic defenses were decreased in pups, while dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data suggest that intrauterine food restriction may disrupt oxidative status, impairing the antioxidant network.

Food restriction during pregnancy alters brain's antioxidant network in dams and their offspring.

Arboviral diseases have a high incidence in Brazil and constitute a serious public health problem. Rocio virus (ROCV) is an arbovirus belonging to the family Flaviviridae. It was responsible for the emergence of an outbreak of encephalitis on the São Paulo state coast in the late 1970s. Although no recent case of this virus has been reported, data suggest the circulation of ROCV throughout the Brazilian territory. Given these indications and the strong presence of fundamental factors for the resurgence of emerging diseases in Brazil, we conducted this study using virtual screenings to identify targets and therapeutic molecules that could be redirected to fight infections related to ROCV. Herein, we demonstrated that the National List of Essential Medicines of the Brazilian Unified Health System (SUS) has several molecules that could be redirected to combat this flavivirus, namely simeprevir, daclatasvir, iloprost, and itraconazole. Among them, itraconazole was found to be an interesting candidate since it interacts with both structural and nonstructural proteins of this virus and it is a strong binder to the NS1 protein, as confirmed by molecular simulations.

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Rocio Virus Encephalitis: In Silico Evidence for Drug Repurposing

Introduction Polyphenols are compounds found in plants that have been extensively studied due to the health benefits of its consumption in adulthood. Meanwhile, recent evidence suggests that polyphenol consumption during pregnancy may not be safe for the fetus. Objective The goal of this study was to evaluate the effect of naringenin supplementation during pregnancy on brain redox homeostasis and mitochondrial activity of the newborn rat. Methods Adult female Wistar rats were divided into two groups: (1) vehicle (1 mL/Kg p.o.) or (2) naringenin (50 mg/Kg p.o.). Naringenin was administered once a day during pregnancy. The offspring were euthanized on postnatal day 7, as well the dams, and brain regions were dissected. Results The offspring cerebellum was the most affected region, presenting increased activity of the mitochondrial electron transport system, allied to increased reactive species levels, lipid peroxidation, and glutathione concentration. The nitric oxide levels suffered structure-dependent alteration, with decreased levels in the pups' cerebellum and increased in the hippocampus. The offspring parietal cortex was not affected, as well as the parameters evaluated in the dams' brains. Conclusion Maternal consumption of naringenin alters offspring cerebellar redox homeostasis, which could be related to adverse effects on the motor and cognitive development in the descendants.

João Pedro Sagini

Papers

Physical Exercise During Pregnancy Prevents Cognitive Impairment Induced by Amyloid-β in Adult Offspring Rats

Food restriction during pregnancy alters brain's antioxidant network in dams and their offspring.

Rocio Virus Encephalitis: In Silico Evidence for Drug Repurposing

Maternal polyphenol intake impairs cerebellar redox homeostasis in newborn rats.