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BACKGROUND: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty‐four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H2O2). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test. RESULTS: The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP. CONCLUSION: Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Caffeine is a widely consumed substance, and there is a discussion about its effects when ingested by women during pregnancy and lactation. We aimed to identify the genotoxic effects of caffeine in female mice that consumed it during pregnancy and lactation periods and its consequences in their offspring. Thirty-six couples of Swiss mice received water or caffeine (0.3 and 1.0 mg/mL) treatment during pregnancy and lactation. The male and female offspring were divided into 12 groups according to the treatment administered to the female mice. Genotoxicity was assessed using the comet assay and the micronucleus test. Both doses of caffeine showed genotoxic effects in pregnant and lactating mice groups compared to groups not administered caffeine. In relation to offspring, it can be observed that females and males of the offspring had low weight in early life. In both female and male offspring, genotoxicity was detected in the blood, liver, and kidney tissues. Thus, from the present study, we can suggest that the caffeine consumed by female mice during the periods of pregnancy and lactation led to genotoxic effects in their offspring. Abbreviations: ANOVA: Analysis of variance; APE1: Apurinic/ apyrimidinic endonuclease 1; CAF: Caffeine; CAPES: Coordination for the Improvement of Higher Education Personnel; CNPq: National Council of Technological and Scientific Development; COBEA: Brazilian College of Animal Experimentation; CREB: Cyclic adenosine monophosphate response element-binding protein; CTR: control; EDTA: Ethylenediaminetetraacetic acid; FAPESC: Santa Catarina Research and Innovation Support Foundation; MN: Micronucleus; MNNCE: Micronucleated normochromatic erythrocytes; MNPCE: Micronucleated polychromatic erythrocytes; PBS: Phosphate-buffered saline; PKA: Protein kinase A; PPGCS: Graduate Program in Health Sciences; SBCAL: Brazilian College of Animal Experimentation; uNESC: university of Southern Santa Catarina; WHO: World Health Organization [ABSTRACT FROM AUTHOR]

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID‐19) patients. Mild and severe COVID‐19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID‐19 patients presented lower frequencies of CD4+CD25+CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high‐differentiated (CD27−CD28−) CD8+ T cells compared with healthy controls. Severe COVID‐19 patients also showed higher frequencies of CD4+CD39+, CD4+CD25−CD39+ (memory T effector cell), and high‐differentiated CD8+ T cells (CD27−CD28−), and diminished frequencies of CD4+CD73+, CD4+CD25+CD39+ mTreg cell, CD8+CD73+, and low‐differentiated CD8+ T cells (CD27+CD28+) in the blood in relation to mild COVID‐19 patients and controls. Moreover, severe COVID‐19 patients presented higher expression of PD‐1 on low‐differentiated CD8+ T cells. Both severe and mild COVID‐19 patients presented higher frequencies of CD4+Annexin‐V+ and CD8+Annexin‐V+ T cells, indicating increased T‐cell apoptosis. Plasma samples collected from severe COVID‐19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID‐19 patients with adenosine reduced the nuclear factor‐κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID‐19 immunopathology through purinergic regulation. [ABSTRACT FROM AUTHOR]

Caregivers of elderly people with neurodegenerative diseases are highly vulnerable to stressful situations and mood disorders due to their work conditions. Stress has been associated with an increased risk of developing depression, and studies have supported that caffeine consumption can act as an independent protective factor for disorder. This study investigated indexes of stress and depression symptoms in caregivers of the elderly with neurodegenerative diseases, their caffeine intake and the association between stress and depressive symptoms with the salivary biomarkers cortisol, nitric oxide and DNA damage. Participants (n = 81) were recruited from the community between July 2018 and April 2019. Stress was assessed using Lipp's Inventory of Stress Symptoms, and depressive symptoms were measured using the Hamilton Depressive Rating Scale. Participants provided a 72-hour recall of their diet to measure caffeine intake. Saliva samples were used to measure cortisol and nitric oxide. DNA damage was measured through micronuclei frequency after swabbing on the buccal mucosa. The majority of caregivers displayed stress and depressive symptoms. Stress was associated with educational level, tobacco use and total DNA damage. The indexes found in this population were not associated with caffeine intake or other salivary biomarkers, indicating that only some salivary molecules could be used as biomarkers for stress-related disorders. Caregivers of the elderly are exposed to stressful situations daily, however, we observed that educational level can reduce the psychological symptoms of stress and thus reduce the negative impact on quality of life. [ABSTRACT FROM AUTHOR]

Studies on caffeine consumption have shown a negative correlation with development of some diseases with subsequent beneficial manifestations. Our aim was to assess the effects of caffeine on peripheral blood and neural tissue DNA in young adult and aged mice. Male Swiss mice (age 2–3 or 16–18 months, respectively) were treated with a caffeine solution (0.3 g/l) for 4 weeks, while controls received water. After the treatments, blood and hippocampal cells (for a comet assay) and femurs (for a micronucleus [MN] test) were collected. The comet assay of peripheral blood and hippocampal cells demonstrated no significant differences between caffeine-treated and control young adult mice in terms of DNA damage index (DI) and frequency. In contrast, when comparing young adult with aged animals, significant differences were observed in DNA damage in blood and hippocampal cells. The differences between aged animals (with or without caffeine) consisted of a significant decrease in DNA DI in the group that received caffeine. In the MN test, an increase in frequency of micronucleated polychromatic (PCE) erythrocytes was noted in aged animals that received water compared to young adult mice. In addition, comparing treated with control aged murine groups, a decrease in frequency of MN was found in PCE erythrocytes of caffeine-treated mice. Chronic caffeine consumption was neither genotoxic nor mutagenic at the dose tested; however, it appears that caffeine actually protected mice from genotoxicity and mutagenicity, consequences attributed to aging. [ABSTRACT FROM PUBLISHER]

Brain tolerance or resistance can be achieved by interventions before and after injury through potential toxic agents used in low stimulus or dose. For brain diseases, the neuroprotection paradigm desires an attenuation of the resulting motor, cognitive, emotional, or memory deficits following the insult. Preconditioning is a well-established experimental and clinical translational strategy with great beneficial effects, but limited applications. NMDA receptors have been reported as protagonists in the adjacent cellular mechanisms contributing to the development of brain tolerance. Postconditioning has recently emerged as a new neuroprotective strategy, which has shown interesting results when applied immediately, i.e. several hours to days, after a stroke event. Investigations using chemical postconditioning are still incipient, but nevertheless represent an interesting and promising clinical strategy. In the present review pre- and postconditioning are discussed as neuroprotective paradigms and the focus of our attention lies on the participation of NMDA receptors proteins in the processes related to neuroprotection. [ABSTRACT FROM AUTHOR]

ObjectiveThis study investigated the influence of ageing – in particular the decrease of gonadal hormone levels during the ageing process – on the memory and the levels of DNA damage in the hippocampus of female rats.MethodsThree groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay.ResultsAccording to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones.ConclusionOur results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy. [ABSTRACT FROM PUBLISHER]

ObjectiveMethylphenidate (MPD) is a drug prescribed for the treatment of attention deficit/hyperactivity disorder and its therapeutic effect is attributed to the inhibition of dopamine.MethodsYoung male Wistar rats were administered MPD (1, 2, 5, or 10 mg/kg) once a day or an intraperitoneal injection of saline for 28 days (chronic treatment) or for 1 day (acute treatment). Two hours after the last administration the animals were decapitated and their striatum was dissected.ResultsIn this work, we show that continued treatment with MPD is capable of modifying the levels of phosphorylation of proteins JNK1/2 (c-Jun amino-terminal kinases 1 and 2) and ERK1/2 (extracellular signal-regulated kinases 1 and 2). Whereas the level of phosphorylation of protein ERK increased significantly, that of proteins JNK1/2 diminished.ConclusionThe alteration in the level of activation of mitogen-activated protein kinases can be a molecular mechanism through which MPD exerts its therapeutic effect. [ABSTRACT FROM AUTHOR]

Neuropeptide S (NPS) is the endogenous ligand of a G-protein-coupled receptor named as NPSR. Behavioral effects have been recently attributed to NPS, i.e. hyperlocomotion, anxiolysis, and wakefulness. However, little is known about the mechanisms by which NPS evokes such biological actions. The present study aimed to investigate the role played by the adenosine A2A and A1 receptors in hyperlocomotion induced by NPS. Spontaneous locomotion was assessed in an activity cage for 30 min in mice acutely treated with caffeine (a nonselective adenosine receptor antagonist), ZM241385 (a selective A2A receptor antagonist), or CPT (a selective A1 receptor antagonist) before NPS challenge (0.1 nmol, i.c.v.), which induce hyperlocomotion in mice. The pretreatment with caffeine (3 mg/kg, i.p.), in an inactive dose per se, prevented the increase in locomotion evoked by NPS. The co-administration of NPS (0.1 nmol, i.c.v.) and ZM241385 (0.1 pmol, i.c.v.) counteracted hyperlocomotion evoked by NPS. The co-administration of NPS and CPT (0.1 pmol, i.c.v.) slightly facilitated the increase in locomotion evoked by NPS alone. In summary, the pharmacological blockade of A2A receptors significantly attenuated the stimulatory effects of NPS. By contrast, the antagonism of A1 receptors facilitated NPS-induced hyperlocomotion in mice, but we cannot rule out a merely additive effect of two stimulatory systems in the brain. Altogether, this is the first evidence of a putative role played by A2A and A1 receptors in modulating hyperlocomotion induced by NPS. [ABSTRACT FROM AUTHOR]

Exercise training has demonstrated cardioprotection effects. However, the exact mechanism behind this effect is not is clear. The present study evaluated the effects of 12 weeks of previous treadmill training on the levels of oxidative damage, antioxidant enzyme activity and injury in the myocardium of rats submitted to infarction induced by isoproterenol (ISO). Isoproterenol treatment (80 mg/kg given over 2 days in two equal doses) caused arrhythmias and 60% mortality within 24 h of the last injection in the control group (C + ISO) group when compared with the saline control group (saline). Creatine Kinase - MB levels were markedly increased in hearts from ISO-treated animals in the C + ISO group. Twelve weeks of treadmill training reduced superoxide production, lipid peroxidation levels and protein carbonylation in these animals, as well as increasing the activities and expressions of SOD and CAT. Previous training also reduced CK-MB levels and numbers of deaths by 40%, preventing the deleterious effects of ISO. Based on the data obtained in this study, it is suggested that 12-week treadmill training increases antioxidant enzymes, decreases oxidative damage and reduces the degree of infarction induced by ISO in the hearts of male rats. [ABSTRACT FROM AUTHOR]