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This study aimed to evaluate the behavioral and energy metabolism parameters in female mice subjected to obesity and offspring deprivation (OD) stress. Eighty female Swiss mice, 40 days old, were weighed and divided into two groups: Control group (control diet, n = 40) and Obese group (high-fat diet, n = 40), for induction of the animal model of obesity, the protocol was based on the consumption of a high-fat diet and lasted 8 weeks. Subsequently, the females were subjected to pregnancy, after the birth of the offspring, were divided again into the following groups (n = 20): Control non-deprived (ND), Control + OD, Obese ND, and Obese + OD, for induction of the stress protocol by OD. After the offspring were 21 days old, weaning was performed and the dams were subjected to behavioral tests. The animals were humanely sacrificed, the brain was removed, and brain structures were isolated to assess energy metabolism. Both obesity and OD led to anhedonia in the dams. It was shown that the structures most affected by obesity and OD are the hypothalamus and hippocampus, as evidenced by the mitochondrial dysfunction found in these structures. When analyzing the groups separately, it was observed that OD led to more pronounced mitochondrial damage; however, the association of obesity with OD, as well as obesity alone, also generated damage. Thus, it is concluded that obesity and OD lead to anhedonia in animals and to mitochondrial dysfunction in the hypothalamus and hippocampus, which may lead to losses in feeding control and cognition of the dams., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity is associated with low-grade chronic inflammation and oxidative stress, affecting the brain's reward system by decreasing dopaminergic neurotransmission. It is known that dopaminergic neurotransmission is also reduced in Parkinson's disease (PD), and high adiposity is considered a risk factor for the development of several neurodegenerative diseases, including PD. This study aimed to assess the effects of obesity on neuroinflammatory and neurochemical parameters in an animal model of reserpine-induced PD. The obese group showed increased inflammation and oxidative damage as well as inhibition of mitochondrial respiratory chain complexes I and II and DNA damage in the evaluated structures. The PD group did not show inflammation or mitochondrial dysfunction but exhibited oxidative damage in the hippocampus. The combination group (obesity + PD) showed reduced inflammation and oxidative stress and increased activity of complexes I and II of the mitochondrial respiratory chain in most of the analyzed structures. On the other hand, obesity + PD caused oxidative damage to proteins in the liver, prefrontal cortex, striatum, and cerebral cortex and oxidative stress in the hypothalamus, resulting in reduced catalase activity. Furthermore, the combination group showed DNA damage in blood, liver, and cerebral cortex. In conclusion, it was observed that the association of obesity and PD did not increase inflammation, oxidative stress, or mitochondrial dysfunction in most of the evaluated structures but increased oxidative damage and induced mechanisms that led to DNA damage in peripheral tissues and brain structures., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex, hippocampus, striatum, cerebral cortex and liver of high-fat diet-induced obese mice. Food intake, body weight, visceral fat weight, and liver weight were also evaluated. Male Swiss mice were divided into control (low-fat purified diet) and obese (high-fat purified diet) groups. After 6 weeks, mice were divided into control + saline, control + C. cardunculus leaf ethanol extract, obese + saline, obese + C. cardunculus leaf ethanol extract. Cynara cardunculus leaf ethanol extract (1600 mg/kg/day) or saline was administered orally for 4 weeks. Brain structures (hypothalamus, hippocampus, prefrontal cortex, striatum and cerebral cortex) and liver were removed. Treatment with C. cardunculus leaf ethanol extract did not affect body weight but did reduce visceral fat. Obesity can cause inflammation and oxidative stress and increase the activity of antioxidant enzymes in brain structures. Treatment with ethanolic extract of C. cardunculus leaves partially reversed the changes in inflammatory damage parameters and oxidative damage parameters and attenuated changes in the antioxidant defense. The C. cardunculus leaf ethanol extract benefited from the brains of obese animals by partially reversing the changes caused by the consumption of a high-fat diet and the consequent obesity. These results corroborate those of studies indicating that the C. cardunculus leaf ethanol extract can contribute to the treatment of obesity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Brazil nut ( Bertholletia excelsa, H.B.K. ) originating from the Amazon region is one of the richest known sources of selenium (Se), a micronutrient that is essential and required for optimal physiological functioning. This mineral presents several health benefits, including improvement of the redox cellular status and maintenance of genomic stability. Knowing that type 2 diabetes mellitus (T2D) is strongly linked to oxidative stress and consequently DNA damage, the aim of this study was to assess the ex vivo antioxidative effects of Se through Brazil nut consumption and its potential in preventing oxidative DNA damage induced by H 2 O 2 . In order to accomplish this, the Comet assay (single-cell gel electrophoresis) was used to measure DNA damage in peripheral blood cells harvested before and after supplementation with Brazil nut. Comet assay was also applied ex vivo to measure the potential of Se to prevent oxidative damage to DNA induced by H 2 O 2 in blood of type 2 diabetes patients collected before and after six months of supplementation with Brazil nut. We found that supplementation with Brazil nuts significantly increased serum Se levels. Furthermore, we observed a significant increase in fasting blood glucose after six months of consuming Brazil nuts; however, no significant effect was observed on the levels of glycated hemoglobin. Finally, we noticed that the cells were more resistant to H 2 O 2 -induced DNA damage after six months of supplementation with Brazil nut. Thus, consumption of Brazil nuts could decrease oxidative DNA damage in T2D patients, probably through the antioxidative effects of Se.

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle ( n  = 6), melanoma + vehicle ( n  = 10), PBS + melatonin ( n  = 6), and melanoma + melatonin ( n  = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.

Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA, which leads to neuronal death. In this way, DNA damage has been implicated in the pathogenesis of neurological disorders, cancer, and aging. Lifestyle factors, such as physical exercise, are neuroprotective and increase brain function by improving cognition, learning, and memory, in addition to regulating the cellular redox milieu. Several mechanisms are associated with the effects of exercise in the brain, such as reduced production of oxidants, up-regulation of antioxidant capacity, and a consequent decrease in nuclear DNA damage. Furthermore, physical exercise is a potential strategy for further DNA damage repair. However, the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown. In this review, we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain. We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage., Competing Interests: None

Epidemiological data from the last decades point to an exponential growth in the number of obese people. Different behavioral factors, mainly associated with food consumption, appear to contribute significantly to its development. Concomitant with increased obesity rates, an increase in the consumption of fructose has been observed; therefore, fructose consumption has been implicated as an important obesogenic factor. However, changes in brain activity due to fructose consumption are possible, especially in relation to hypothalamic satiety mechanisms. In addition, the obese state may provide an environment of chronic inflammation and further contribute to the discontinuation of satiety mechanisms in the hypothalamus. We briefly review the intrinsic alterations to the increased adipose tissue, its connections with the hypothalamus in the control of energy signaling mechanisms and, consequently, the participation of fructose as a co-adjuvant or trigger. Presenting the current context with clinical trials involving human and animal studies, we seek to contribute to a better understanding of the role of fructose in the progression of obesity., (© 2020 Wiley Periodicals LLC.)

The consumption of fructose during pregnancy can cause hyperglycaemia and may stimulate production of reactive oxygen species; however, there are only a few studies reporting whether fructose consumption during pregnancy causes DNA damage. Therefore, the aim of this study was to evaluate the effects of fructose consumption on genetic and biochemical parameters in Swiss mice treated during pregnancy and lactation. For this, 15 couples of 60-day-old Swiss mice were divided into three groups of five couples: negative control (water) and two fructose groups (fructose dose of 10%/l and 20%/l). During this period, we evaluated food consumption, energy efficiency and body weight. Samples of blood were collected from the females before copulation, after the 15th day of conception and on the 21st day after the lactation period, for the glycaemic and lipid profiles as well as comet assay and micronucleus (MN) test. Comet assay and MN test evaluate DNA damage and clastogenicity, respectively. In the gestation and lactation period, the two fructose doses tested showed DNA damage as observed in the comet assay, which is associated with an increase in dietary intake, body weight, lipid profile and fasting glycaemia in females. Thus, it can be suggested that the high consumption of fructose during these periods is harmful for pregnancy and lactation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina. Participants received 4000 IU of vitamin D3 (25(OH)D) supplementation daily for 8 weeks. Blood samples were collected at the beginning and at the end of the supplementation, and 4 weeks after the end of supplementation. The glycidic and lipid profiles [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglycerides], oxidative stress, DNA damage and 25(OH)D levels were evaluated. Vitamin D3 supplementation for 8 weeks showed enough to significantly increase blood levels of 25(OH)D. A significant difference in lipid profile was observed only in non-HDL cholesterol. Significant changes were observed in glucose homeostasis (fasting glucose and serum insulin) and, in addition, a reduction in the parameters of oxidative stress and DNA damage. There was a significant reduction in the values of 25(OH)D 4 weeks after the end of the supplementation, but levels still remained above baseline. Use of vitamin D supplementation can be an ally in the health modulation of patients with type 2 diabetes mellitus., (© The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to evaluate the DNA damage in peripheral lymphocytes and the frequencies of CD8+ T cells expressing CD25, CD28 and CD45ro in aged individuals with inverted CD4:CD8 ratio. Blood samples of elderly individuals (aged >65) with normal CD4:CD8 ratio (n = 8) and inverted CD4:CD8 ratio (n = 8) were collected to identify the expression of CD25+, CD28+ and CD45ro+ in CD8+ T cells. DNA damage index was evaluated by the alkaline comet assay which was performed in lymphocytes treated with different concentrations of methyl methanesulfonate (MMS) (control non-treatment, 2 × 10 -5  M, 4 × 10 -5  M) for 1, 2 or 24 h. Elderly individuals with inverted CD4:CD8 ratio presented low frequency of CD8+ CD28+. Moreover, low DNA damage was observed in lymphocytes of elderly with inverted CD4:CD8 ratio in different doses of MMS. Aged individuals with inverted CD4:CD8 ratio presented lower DNA damage events in peripheral lymphocytes, suggesting a resistance for cell death in T cells of individuals with immune risk profile., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata , mainly in genetic level, this work aims to evaluate, in vitro , the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

The aim of the present study was to evaluate the genotoxic effect of lettuce ( Lactuca sativa L.), beet ( Beta vulgaris L.), broccoli ( Brassica oleracea var. italica ), and kale ( Brassica oleracea var. acephala ) grown in vegetable garden built on the deposits of coal tailings. For this, we used 72 healthy male Swiss albino mice that received juice from the vegetables in an acute or chronic treatment. Using comet assay, we determined that acute administration of the juices of all vegetables from the coal-mining area was genotoxic, and increased the DNA damage in the blood, liver, and cerebral cortex of mice. Therefore, the present data suggest that intake of vegetables cultivated over coal waste results in an increase in DNA damage in some organs; this situation may pose a risk to health.

Hibiscus acetosella was shown to exert beneficial effects in humans and animal models however, the effects of this plant on DNA are unknown. The aim of this study was to determine the antigenotoxic and antimutagenic effects of H. acetosella extracts on alkylating agent methyl methanesulfonate (MMS) in vivo in mice. Initially, we performed analysis of phenolic compounds in extracts of H. acetosella by high-performance liquid chromatography (HPLC). Next, mice were divided into 8 groups and treated with distilled water or plant extract (0.1 ml/10 g) by gavage for 15 days, followed by intraperitoneal (ip) administration of saline solution or MMS (40 mg/Kg b.w) on day 16. Caffeic acid, following by gallic acid, gallocatechin, coumaric acid, and 3,4-dihydroxybenzoic acid were found to be present in extracts of H. acetosella leaves. In peripheral blood analysis of groups receiving pretreatment with H. acetosella at doses of 50 or 100 mg/kg plus MMS decreased DNA damage as evidenced by comet assay and Micronucleus assays relative to MMS alone. These results suggested that H. acetosella extracts exerted protective effects dose dependent against genotoxicity and mutagenicity induced by alkylating agents.

Skeletal muscle aging is associated with loss of mass, function, and strength-a condition known as sarcopenia. It has been reported that sarcopenia can be attenuated by physical exercise. Therefore, we investigated whether 2 different physical exercise protocols could modulate and induce changes in oxidative and inflammatory parameters, as well as in BDNF and DNA repair enzyme levels in skeletal muscle tissue of aged rats. Aging Wistar rats performed treadmill or strength training for 50 min 3 to 4 times a week for 8 weeks. Strength training decreased 2',7'-dichlorofluorescein (DCFH) oxidation (P = 0.0062); however, nitric oxide, protein deglycase DJ-1, and tumor necrosis factor alpha (TNF-α) levels increased after aerobic training (P = 0.04, P = 0.027 and P = 0.009, respectively). Both exercise protocols increased superoxide dismutase (SOD) and catalase (CAT) activity (P = 0.0017 and P = 0.0326) whereas the activity of glutathione (GSH) (P = 0.0001) was decreased. Brain-derived neurotropic factor (BDNF) levels were not affected by exercise, but 8-oxoguanine glycosylase (OGG1) decreased after strength training (P = 0.0007). In conclusion, oxidative parameters showed that skeletal muscle adapt to increased ROS levels, reducing the risk of free radical damage to the tissue after both exercise protocols. These results show that the effects of physical exercise on skeletal muscle are mediated in an exercise type-dependent manner., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Tityus serrulatus is the scorpion associated with the most severe cases of scorpion envenoming in Brazil. However, there are no studies reporting the genotoxic effects of this venom in natural or experimental envenomations. It is well known that DNA-damage responses are providing opportunities for improving disease detection and management. In this study was evaluating the genotoxicity of the T. serrulatus venom in different organs (hippocampus, cortex, striatum, blood, heart, lung, liver and kidney) and periods in mice experimentally envenomed. ELISA and the Comet assays were used to quantification of venoms antigens and DNA damage, respectively. Forty-eight Swiss mice were divided into five groups and 0.5 DL 50 of T. serrulatus venom (0.90 mg/kg) was administered intraperitoneally in each animal. Euthanasia was performed by cervical dislocation in the period of 0h (control group) 1h, 2h, 6h and 12h, where it the tissues were removed. The results showed high DNA damage in all structures analyzed, suggesting that T. serrulatus venom presented genotoxic activity or some secondary effect generated by venom injection. In the ELISA test, toxic circulant antigens were verified in practically all organs at the time intervals analyzed. Therefore, the distribution of the venom changes from organ to organ. We conclude that scorpion envenoming affects DNA in all organs analyzed even when the venom concentration is lower or no detectable, DNA damage persists., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75 NTR receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1β. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.

Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a deficiency of the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. The affected patients present severe neurological symptoms, such as coma and seizures, as well as edema and cerebral atrophy. Considering that the mechanisms of the neurological symptoms presented by MSUD patients are still poorly understood, in this study, protein levels of apoptotic factors are measured, such as Bcl-2, Bcl-xL, Bax, caspase-3 and -8 in hippocampus and cerebral cortex of rats submitted to acute administration of branched-chain amino acids during their development. The results in this study demonstrated that BCAA acute exposure during the early postnatal period did not significantly change Bcl-2, Bcl-xL, Bax and caspase-8 protein levels. However, the Bax/Bcl-2 ratio and procaspase-3 protein levels were decreased in hippocampus. On the other hand, acute administration of BCAA in 30-day-old rats increase in Bax/Bcl-2 ratio followed by an increased caspase-3 activity in cerebral cortex, whereas BCAA induces apoptosis in hippocampus through activation and cleavage of caspase-3 and -8 without changing the Bax/Bcl-2 ratio. In conclusion, the results suggest that apoptosis could be of pivotal importance in the developmental neurotoxic effects of BCAA. In addition, the current studies also suggest that multiple mechanisms may be involved in BCAA-induced apoptosis in the cerebral cortex and hippocampus.

Hereditary fructose intolerance (HFI) is an autosomal-recessive disorder characterized by fructose and fructose-1-phosphate accumulation in tissues and biological fluids of patients. This disease results from a deficiency of aldolase B, which metabolizes fructose in the liver, kidney, and small intestine. We here investigated the effect of acute fructose administration on the activities of mitochondrial respiratory chain complexes, succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) in cerebral cortex, liver, kidney, and skeletal muscle of male 30-day-old Wistar rats. The rats received subcutaneous injection of sodium chloride (0.9%; control group) or fructose solution (5 μmol/g; treated group). One hour later, the animals were euthanized and the cerebral cortex, liver, kidney, and skeletal muscle were isolated and homogenized for the investigations. Acute fructose administration increased complex I-III activity in liver. On the other hand, decreased complexes II and II-III activities in skeletal muscle and MDH in kidney were found. Interestingly, none of these parameters were affected in vitro. Our present data indicate that fructose administration elicits impairment of mitochondrial energy metabolism, which may contribute to the pathogenesis of the HFI patients.

Hereditary fructose intolerance is an autosomal recessive disorder characterized by the accumulation of fructose in tissues and biological fluids of patients. The disease results from a deficiency of aldolase B, responsible for metabolizing fructose in the liver, kidney, and small intestine. We investigated the effect of acute fructose administration on oxidative stress and neuroinflammatory parameters in the cerebral cortex of 30-day-old Wistar rats. Animals received subcutaneous injection of sodium chloride (0.9 %) (control group) or fructose solution (5 μmol/g) (fructose group). One hour later, the animals were euthanized and the cerebral cortex was isolated. Oxidative stress (levels of thiobarbituric acid-reactive substances (TBA-RS), carbonyl content, nitrate and nitrite levels, 2',7'-dihydrodichlorofluorescein (DCFH) oxidation, glutathione (GSH) levels, as well as the activities of catalase (CAT) and superoxide dismutase (SOD)) and neuroinflammatory parameters (TNF-α, IL-1β, and IL-6 levels and myeloperoxidase (MPO) activity) were investigated. Acute fructose administration increased levels of TBA-RS and carbonyl content, indicating lipid peroxidation and protein damage. Furthermore, SOD activity increased, whereas CAT activity was decreased. The levels of GSH, nitrate, and nitrite and DCFH oxidation were not altered by acute fructose administration. Finally, cytokines IL-1β, IL-6, and TNF-α levels, as well as MPO activity, were not altered. Our present data indicate that fructose provokes oxidative stress in the cerebral cortex, which induces oxidation of lipids and proteins and changes of CAT and SOD activities. It seems therefore reasonable to propose that antioxidants may serve as an adjuvant therapy to diets or to other pharmacological agents used for these patients, to avoid oxidative damage to the brain.