21 research outputs found
Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology
The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its "dark side" role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer
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Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans
Morphine withdrawal increases metabotropic glutamate 2/3 receptors expression in nucleus accumbens
We examined the effects of chronic morphine treatment and withdrawal on the expression of metabotropic glutamate (mGlu)1, mGlu5, and mGlu2/3 receptors in the nucleus accumbens and caudate putamen. Rats received a 14-day morphine treatment (escalating doses from 10 to 140 mg/kg). Receptor density was evaluated after chronic treatment and after 1, 3, and 14 days of withdrawal. mGlu1 and mGlu5 expression in the nucleus accumbens and in the caudate putamen was not affected by any of the experimental manipulations. In contrast, mGlu2/3 receptors in the nucleus accumbens, but not in the caudate putamen, increased at day 1, 3, and 14 of withdrawal. We suggest that an increased expression of mGlu2/3 receptors in the nucleus accumbens might contribute to the symptoms of morphine withdrawal
Sleep, anxiety and psychiatric symptoms in children with Tourette syndrome and tic disorders
Objective: The current study evaluated the relationship between tic, sleep disorders and
specific psychiatric symptoms (anxiety, depression, obsessive compulsive symptoms).
Methods: Assessment of 36 consecutive children and adolescents with tic disorders
included: the Yale Global Tic Severity Scale (YGTSS) to assess the severity of tic symptoms;
the Self-administered scale for children and adolescents (SAFA) to evaluate the psychopathological
profile; a specific sleep questionnaire consisting of 45 items to assess the
presence of sleep disorders.
An age and sex-matched control group was used for comparisons.
Results: Sleep was significantly more disturbed in patients with tic disorders than in controls.
Difficulties in initiating sleep and increased motor activity during sleep were the most
frequent sleep disturbances found in our sample. Patients showed also symptoms of
anxiety (SAFA A), depressed mood (SAFA D) and doubteindecision (SAFA O). Additionally,
difficulties in initiating sleep resulted associated with other SAFA subscales relative to
obsessiveecompulsive symptoms and depression symptoms. Furthermore, anxiety
symptoms (SAFA A) resulted associated with increased motor activity during sleep.
Conclusions: Findings confirm literature studies reporting high frequency of sleep problems,
anxiety and other psychopathological symptoms in patients with tic disorders, and support
the hypothesis that intrusive thoughts and other emotional disturbances might disrupt the
sleep onset of these patients. These results suggest the importance of a thorough assessment
of sleep and psychiatric disturbances in patients with tic disorders
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Anabolic androgenic steroids influence the expression of Brain Nerve Growth Factor in the rat
Repeated anabolic androgenic steroid treatment causes antidepressant-reversible alterations of the hypothalamic - pituitary - adrenal axis, BDNF levels and behavior
Abuse of anabolic androgenic steroids (AASs) is frequently associated with changes in mood, including depression. However, the nature of this association is still largely unexplored. As a model of AAS abuse, we used male adult rats injected for 4 weeks with either nandrolone or stanozolol at daily doses (5 mg/kg, s.c.) that are considered equivalent to those abused by humans on a milligram per kilogram of body weight basis. AAS treatment reduced levels of brain-derived neurotrophic factor in the hippocampus and prefrontal cortex, reduced the expression of low-affinity glucocorticoid receptors in the hippocampus, and increased morning trough basal plasma corticosterone levels. All these changes have been related to the pathophysiology of major depressive disorder. Accordingly, rats treated with nandrolone or stanozolol showed an increased immobility time in the forced swim test, which is widely used for the screening of antidepressant drugs. All effects produced by AASs were prevented by co-administration with the classical antidepressant, chlorimipramine. The evidence that supraphysiological doses of AASs induce changes indicative of a depressive state in normal rats, raises the concern that AAS abuse in humans may cause depression regardless of exposure to stress or other risk factors. (C) 2010 Elsevier Ltd. All rights reserved
Prenatal Methylmercury Exposure: Effects on Stress Response During Active Learning
The long-term impact of prenatal methylmercury (MeHg) exposure on the stress response during active learning was investigated. Pregnant rats were gavage fed MeHg (8 mg/kg) on gestational day 15. Ninety-day-old rats born to both MeHg- and saline-treated dams were subjected to an active avoidance test. The active avoidance-experienced rats (AAERs) with prenatal exposure to MeHg showed significant impairment in learning ability and exhibited higher levels of corticosterone than the untreated AAERs. The present findings suggest that the abnormal increase in plasma corticosterone levels could contribute to the poor performance of MeHg-treated AAERs in this learning task
Social isolation selectively reduces hippocampal brain-derived neurotrophic factor without altering plasma corticosterone
It is well known that housing conditions may alter several physiological and behavioral parameters. In this study, we have investigated whether a prolonged period of partial social isolation can modify central brain-derived neurotrophic (BDNF) concentrations. Male Sprague-Dawley rats were singly housed for 8 weeks before hippocampi, prefrontal cortices and striata were collected for BDNF determination. Compared to rats housed two per cage, isolated rats showed a significant reduction on BDNF protein concentrations in the hippocampus while no changes were observed in the other brain regions examined. Moreover, housing condition had no effect on basal plasma corticosterone. On the basis of the proposed etiological participation of reduced central BDNF concentrations in affective disorders, our results would candidate social isolation as a model for the study of antidepressant treatments. (c) 2006 Elsevier B.V. All rights reserved
Nutritional Mushroom Treatment in Meniere’s Disease with Coriolus versicolor: A Rationale for Therapeutic Intervention in Neuroinflammation and Antineurodegeneration
Meniere’s disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus-treated group. This was paralleled by a significant (p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection