Obesity and Depression: Common Link and Possible Targets.

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments.

Unveiling the interplay of AMPK/SIRT1/PGC-1α axis in brain health: Promising targets against aging and NDDs.

The escalating prevalence of neurodegenerative diseases (NDDs) within an aging global population presents a pressing challenge. The multifaceted pathophysiological mechanisms underlying these disorders, including oxidative stress, mitochondrial dysfunction, and neuroinflammation, remain complex and elusive. Among these, the AMPK/SIRT1/PGC-1α pathway emerges as a pivotal network implicated in neuroprotection against these destructive processes. This review sheds light on the potential therapeutic implications of targeting this axis, specifically emphasizing the promising role of flavonoids in mitigating NDD-related complications. Expanding beyond conventional pharmacological approaches, the exploration of non-pharmacological interventions such as exercise and calorie restriction (CR), coupled with the investigation of natural compounds, offers a beacon of hope. By strategically elucidating the intricate connections within these pathways, this review aims to pave the ways for novel multi-target agents and interventions, fostering a renewed optimism in the quest to combat and manage the debilitating impacts of NDDs on global health and well-being.

Xanthine Oxidoreductase in the Pathogenesis of Endothelial Dysfunction: An Update.

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the formation of uric acid (UA) and is involved in the generation of reactive oxygen species (ROS). Overproduction of ROS has been linked to the pathogenesis of hypertension, atherosclerosis, and cardiovascular disease, with multiple studies over the last 30 years demonstrating that XOR inhibition is beneficial. The involvement of XOR and its constituents in the advancement of chronic inflammation and ROS, which are responsible for endothelial dysfunction, is the focus of this evidence-based review. An overabundance of XOR products and ROS appears to drive the inflammatory response, resulting in significant endothelium damage. It has also been demonstrated that XOR activity and ED are connected. Diabetes, hypertension, and cardiovascular disease are all associated with endothelial dysfunction. ROS mainly modifies the activity of vascular cells and can be important in normal vascular physiology as well as the development of vascular disease. Suppressing XOR activity appears to decrease endothelial dysfunction, probably because it lessens the generation of reactive oxygen species and the oxidative stress brought on by XOR. Although there has long been a link between higher vascular XOR activity and worse clinical outcomes, new research suggests a different picture in which positive results are mediated by XOR enzymatic activity. Here in this study, we aimed to review the association between XOR and vascular endothelial dysfunction. The prevention and treatment approaches against vascular endothelial dysfunction in atherosclerotic disease.

Andrographolide protect against lipopolysacharides induced vascular endothelium dysfunction by abrogation of oxidative stress and chronic inflammation in Sprague-Dawley rats.

The development of heart disease involves interconnected factors such as oxidative stress, inflammation, and vascular dysfunction. Andrographolide (AG), known for its potent antioxidant and anti-inflammatory properties, has the potential to counteract lipopolysaccharides (LPS)-induced endothelial dysfunction by reducing oxidative stress and inflammation. Our research aimed to investigate the effects of AG on alleviating vascular endothelium dysfunction, oxidative stress, and inflammation in an experimental model induced by LPS. To create chronic vascular endothelium dysfunction, inflammation, and oxidative stress, rats received weekly injections of LPS via their tail vein over a 6-week period. The study evaluated the therapeutic effects of orally administered AG (50 mg/kg/day) on diseased conditions. We conducted aortic histology and measured nitric oxide (NO) thresholds, superoxide dismutase (SOD) activity, constitutive nitric oxide (cNOS) activity, and inducible nitric oxide (iNOS) levels, alongside several inflammatory biomarkers. To evaluate endothelial dysfunction, we assessed endothelium-dependent and endothelium-independent vasorelaxation in aortas through histopathological and various immunoassays examinations. Vascular Endothelial inflammatory activity was consequently enhanced in LPS groups animals when compared to normal control, also endothelial performance were dependently improved by AG therapy. IL-1ß and tumors necrosis factor levels in the aorta decreased in a dose-dependent manner after exogenous AG delivery to LPS-treated rats. However, in current research work aortic SOD activity, NO levels, and cNOS activity increased, whereas aortic malondialdehyde levels and iNOS activity decreased after the AG treatment. These findings suggest that long-term AG therapy could be considered as a potential therapy to avoid vascular endothelial dysfunction and major nonobstructive coronary artery disease.

Alpha-Lipoic acid alleviates imidacloprid-induced neuro-behavioral deficits in rats via Nrf2/HO-1 pathway.

Imidacloprid (IMI), a widely used pesticide in agriculture and a potential food contaminant, poses significant health concerns. This study sought to comprehensively evaluate its neurotoxic effects while investigating the potential protective role of alpha-lipoic acid (ALA), a naturally occurring dietary antioxidant renowned for its capacity to combat oxidative stress, support cardiovascular health, and maintain optimal nerve function. In this study, 28 rats were divided evenly into four groups and administered oral treatments of corn oil, IMI, IMI + ALA, and ALA, respectively. The results of the study indicated that rats exposed to IMI exhibited significant neurobehavioral impairments, decreased levels of antioxidant enzymes and acetylcholinesterase activity, reduced expression of HO-1 and Nrf2, and increased levels of pro-inflammatory cytokines like IL-6 and TNF-α in their hippocampal tissues. Furthermore, histopathological analysis of the brain tissues, specifically cortex and hippocampus, from the IMI-treated group revealed varying degrees of neuronal degeneration. In contrast, rats co-administered ALA alongside IMI showed noticeable improvements in all the assessed toxicological parameters. This study underscores the vital significance of ALA as a potential therapeutic adjunct in mitigating the adverse neurobehavioral consequences of insecticide exposure. By harnessing the Nrf2/HO-1 pathway, ALA demonstrates its ability to shield against IMI-induced neurotoxicity, offering a promising avenue for enhancing public health and safety. As a result, our findings advocate for the incorporation of ALA as a daily dietary supplement to fortify resilience against oxidative stress-related neurobehavioral deficits linked to pesticide exposure, thereby advancing our understanding of neuroprotection strategies in the face of environmental challenges.

Unlocking the therapeutic potential of natural stilbene: Exploring pterostilbene as a powerful ally against aging and cognitive decline.

The therapeutic potential of natural stilbenes, with a particular focus on pterostilbene (PTE), has emerged as a promising avenue of research targeting age-associated conditions encompassing cardiovascular diseases (CVD), diabetes mellitus (DM), and cognitive decline. This comprehensive investigation delves into the intricate mechanisms through which PTE, a polyphenolic compound abundant in grapes and blueberries, exerts its advantageous effects as an anti-aging agent. Central to its action is the modulation of hallmark aging processes, including oxidative damage, inflammatory responses, telomere attrition, and cellular senescence. PTE's ability to effectively penetrate the blood-brain barrier amplifies its potential for safeguarding neural health, thereby facilitating the regulation of neuronal signalling cascades, synaptic plasticity, and mitochondrial functionality. Through engagement with sirtuin proteins, it orchestrates cellular resilience, longevity, and metabolic equilibrium. Encouraging findings from preclinical studies portray PTE as a robust candidate for counteracting age-linked cognitive decline, augmenting memory consolidation, and potentially ameliorating neurodegenerative maladies such as Alzheimer's disease (AD). The synthesis of current scientific insights accentuates the promising translational prospects of PTE as a potent, naturally derived therapeutic agent against cognitive impairments associated with aging. Consequently, these collective findings lay a solid groundwork for forthcoming clinical inquiries and innovative therapeutic interventions in this realm.

Mitochondrial dysfunction in the pathogenesis of endothelial dysfunction.

Cardiovascular diseases (CVDs) are a matter of concern worldwide, and mitochondrial dysfunction is one of the major contributing factors. Vascular endothelial dysfunction has a major role in the development of atherosclerosis because of the abnormal chemokine secretion, inflammatory mediators, enhancement of LDL oxidation, cytokine elevation, and smooth muscle cell proliferation. Endothelial cells transfer oxygen from the pulmonary circulatory system to the tissue surrounding the blood vessels, and a majority of oxygen is transferred to the myocardium by endothelial cells, which utilise a small amount of oxygen to generate ATP. Free radicals of oxide are produced by mitochondria, which are responsible for cellular oxygen uptake. Increased mitochondrial ROS generation and reduction in agonist-stimulated eNOS activation and nitric oxide bioavailability were directly linked to the observed change in mitochondrial dynamics, resulting in various CVDs and endothelial dysfunction. Presently, the manuscript mainly focuses on endothelial dysfunction, providing a deep understanding of the various features of mitochondrial mechanisms that are used to modulate endothelial dysfunction. We talk about recent findings and approaches that may make it possible to detect mitochondrial dysfunction as a potential biomarker for risk assessment and diagnosis of endothelial dysfunction. In the end, we cover several targets that may reduce mitochondrial dysfunction through both direct and indirect processes and assess the impact of several different classes of drugs in the context of endothelial dysfunction.

A shift in focus towards precision oncology, driven by revolutionary nanodiagnostics; revealing mysterious pathways in colorectal carcinogenesis.

Multiple molecular mechanisms contribute to the development of colorectal cancer (CRC), with chromosomal instability (CIN) playing a significant role. CRC is influenced by mutations in several important genes, including APC, TP53, KRAS, PIK3CA, BRAF, and SMYD4. The three molecular subtypes of this disease are CIN, MSI-H, and CIMP (CpG-island phenotype). p53 dysfunction and aberrant Wnt signalling are common characteristics of CRC carcinogenesis. Despite advances in conventional therapy, metastatic CRC remains difficult to treat due to toxicity and resistance. Theranostics for cancer could significantly benefit from nanotechnology, as it would enable more targeted, individualised care with fewer side effects. Utilising functionalized nanoparticles has enabled MRI-guided gene therapy, magnetic hyperthermia, chemotherapy, immunotherapy, and photothermal/photodynamic therapy, thereby radically modifying the way cancer is treated. Active targeting using ligands or peptides on nanoparticles improves the delivery of drugs to cancer cells. Nanostructures such as drug peptide conjugates, chitosan nanoparticles, gold nanoparticles, carbon nanotubes, mesoporous silica-based nanoparticles, silver nanoparticles, hybrid lipid-polymer nanoparticles, iron oxide nanoparticles, and quantum dots may enable targeted drug delivery and enhanced therapeutic efficacy against CRC. Nanomedicines are presently being evaluated in clinical trials for the treatment of colorectal cancer, with the promise of more effective and individualised therapies. This article examines current nanomedicine patents for CRC, including the work of Delta-Fly, Merrimack, and Pfenning, Meaning & Partner, among others. In terms of future nanomedicine research and development, ligand production, particle size, and clearance are crucial factors. Lastly, the numerous nanostructures utilized in nanomedicine for targeted drug administration and diagnostics indicate optimistic prospects for enhancing CRC treatment. The successes of nanomedicine research and development for existing colon cancer treatments are also highlighted in this review.

The neuroprotective effect of ascorbic acid against imidacloprid-induced neurotoxicity and the role of HO-1 in mice.

Imidacloprid (IMI) is not only a neurotoxic agricultural pesticide but also a possible food contaminant. The aims of this study were to (1) explore the relationship between recurrent IMI administration and neuronal toxicity in mice and (2) evaluate the potential neuroprotective effect of ascorbic acid (AA), a substance with significant free radical scavenger and having property to block the inflammatory pathways. Mice were categorized as naïve controls (administered vehicles for 28 days); the IMI-treatment animal group (administered po 45-mg/kg body weight of IMI per day for 28 days); and the IMI + AA treatment animal group (administered the same IMI dose + 200 mg/kg of AA orally for 28 days). On day 28, memory losses were assessed using the Y-maze and novel target identification behavioral tests. Mice were sacrificed 24 h after the final IMI treatments, as well as hippocampus tissues, were utilized to determine histological assessments, oxidative stress biomarkers, and Heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels. The findings demonstrated that IMI-treated mice had substantial impairment of spatial and non-spatial memory functions, as well as reduced antioxidant enzyme and acetylcholinesterase activity. The AA neuroprotective action was achieved through the suppression of the HO-1 expression as well as the stimulation of Nrf2 expression in hippocampal tissues. In summary, recurrent IMI exposure causes oxidative stress and neurotoxicity in mice, and the administration of AA significantly reduces the IMI toxicity possibly by the activation of the HO-1/Nrf2 pathway.

4-Methylesculetin ameliorates LPS-induced depression-like behavior through the inhibition of NLRP3 inflammasome.

The pathophysiology of depression is heavily dependent on inflammation. Evidence suggests that the etiology of depression is linked with NLRP3 inflammasome-induced inflammation. Therefore, blocking the activated NLRP3 inflammasome may be beneficial for treating depression. Due to the limitations of currently available antidepressants, it is necessary to develop novel, safe, and affordable drugs for the treatment of depression. A natural coumarin derivative named 4-methylesculetin (4-MESC) possesses anti-inflammatory properties. However, the role of 4-MESC as an antidepressant has not been elucidated. Therefore, in this study, we explored the antidepressant-like effects of 4-MESC and its underlying molecular mechanism through the modulation of the NLRP3 inflammasome. The docking and molecular dynamic simulation studies revealed that 4-MESC has a higher affinity for the NLRP3 PYD. Blood-brain barrier permeability was confirmed using the SwissADME pharmacokinetic tool. High doses (50 mg/kg) of 4-MESC significantly reduced the immobility duration in the tail-suspension test (TST) and forced swim test (FST) without changing the overall locomotor activity in the female Swiss albino mice that were subjected to lipopolysaccharide (LPS). LPS-induced pro-inflammatory cytokines such as IL-6 and TNF-α were reduced in serum and brain tissues using 4-MESC. 4-MESC's neuroprotective effects are mediated by increased brain-derived neurotrophic factor (BDNF) and decreased cortisol levels. 4-MESC markedly reduced LPS-induced elevated levels of ROS and lipid peroxidation (malondialdehyde levels) and enhanced the superoxide dismutase (SOD) activity and glutathione levels, which revealed its anti-oxidant potential against oxidative stress. 4-MESC diminished the expression levels of NF-κBp65, IL-6, NLRP3, caspase-1, gasdermin D, and IL-1ß in the hippocampus. These findings demonstrated that 4-MESC exhibited antidepressant-like effects by inhibiting the NLRP3 inflammasome. However, other antidepressant mechanisms might also be involved which require further studies.

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1.

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. However, the mechanism involving LPS-induced MCP-1, interleukins, and oxidative stress together is not well demonstrated. Serratiopeptidase (SRP) has been widely used for its anti-inflammatory effects. In this research study, our intention is to establish a potential drug candidate for vascular inflammation in cardiovascular disorder conditions. We used BALB/c mice because this is the most successful model of vascular inflammation, suggested and validated by previous research findings. Our present investigation examined the involvement of SRP in vascular inflammation caused by lipopolysaccharides (LPSs) in a BALB/c mice model. We analyzed the inflammation and changes in the aorta by H&E staining. SOD, MDA, and GPx levels were determined as per the instructions of the kit protocols. ELISA was used to measure the levels of interleukins, whereas immunohistochemistry was carried out for the evaluation of MCP-1 expression. SRP treatment significantly suppressed vascular inflammation in BALB/c mice. Mechanistic studies demonstrated that SRP significantly inhibited the LPS-induced production of proinflammatory cytokines such as IL-2, IL-1, IL-6, and TNF-α in aortic tissue. Furthermore, it also inhibited LPS-induced oxidative stress in the aortas of mice, whereas the expression and activity of monocyte chemoattractant protein-1 (MCP-1) decreased after SRP treatment. In conclusion, SRP has the ability to reduce LPS-induced vascular inflammation and damage by modulating MCP-1.

NLRP3 inflammasome in depression: A review.

The present article provides a detailed concept of the role of NLRP3 inflammasome in the pathophysiology of depression-like chronic diseases where inflammation and release of various cytokines plays a pivotal role in exaggerating the condition. The various pathways involved in NLRP3 activation are the main target of NLRP3 inhibitors for the therapeutic management of depression as per the recent clinical and research studies conducted so far. Further various drug inhibitors for NLRP3 available in preclinical and clinical trials have been discussed in detail. Hence, blockage of the action of NLRP3 inflammasome is crucial to anticipate the inflammatory cytokine release from the mediators that contributes to cause depression.

Nutritional Aspects of People Living with HIV (PLHIV) Amidst COVID-19 Pandemic: an Insight.

Purpose of Review: This review elaborates the role of malnutrition in PLHIV (people living with HIV) in the context of COVID-19 and emphasis the need of supplementation, dietary intervention, and nutritional counselling in the post-COVID era. One of the most critical challenges among HIV/AIDS patients is malnutrition since it weakens the immune system and increases risk to opportunistic infections. In HIV (human immunodeficiency virus) infection, weight loss is prevalent due to reduced nutritional consumption, malabsorption, abnormal metabolism, and antiretroviral therapy. Sufficient nutrition is required for optimal immune function, as a result, food therapy is now considered an important adjuvant in the treatment of HIV patients. Recent Findings: Nutritional intervention, such as the use of dietary supplements, can help to prevent nutrient deficiency, lowering the death risk among malnourished HIV population. Immunocompromised individuals are at very high risk for COVID-19 and malnutrition increases the risk of infection by multiple folds. Interventions, such as nutrition education and counselling are important, to improve the condition of HIV Patients by optimising their nutritional status. Summary: A balanced diet should be one of the most important priorities in preventing PLHIV against the potentially deadly consequences of COVID-19. It is to be ensured that HIV-positive persons continue to get enough and appropriate assistance, such as nutrition and psychological counselling, in the context of COVID-19 infection. The use of telemedicine to maintain nutritional intervention can be beneficial. To meet their nutritional needs and minimise future difficulties, PLHIV infected with COVID-19 should get specialised nutritional education and counselling.

Advanced Glycation End Products: key player of the pathogenesis of atherosclerosis.

Atherosclerosis is the most common type of cardiovascular disease, and it causes intima thickening, plaque development, and ultimate blockage of the artery lumen. Advanced glycation end products (AGEs) are thought to have a role in the development and progression of atherosclerosis. there is developing an enthusiasm for AGEs as a potential remedial target. AGES mainly induce arterial damage and exacerbate the development of atherosclerotic plaques by triggering cell receptor-dependent signalling. The interplay of AGEs with RAGE, a transmembrane signalling receptor present across all cells important to atherosclerosis, changes cell activity, boosts expression of genes, and increases the outflow of inflammatory compounds, resulting in arterial wall injury and plaque formation. Here in this review, function of AGEs in the genesis, progression, and instability of atherosclerosis is discussed. In endothelial and smooth muscle cells, as well as platelets, the interaction of AGEs with their transmembrane cell receptor, RAGE, triggers intracellular signalling, resulting in endothelial damage, vascular smooth muscle cell function modification, and changed platelet activity.

Protective Effect of CP690550 in MPTP-Induced Parkinson's Like Behavioural, Biochemical and Histological Alterations in Mice.

Janus-activated kinases (JAKs) are well known to play a physiological as well as pathological role in several disease conditions such as autoimmune disorders. The present study evaluated the therapeutic potential of CP690550 (pan-JAK inhibitor) in 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) model of Parkinson's disease. Intrastriatal administration of MPTP (30 micromol in 2 microl) produced a significant alteration in behavioural (bar test and block test). Biochemical investigations in serum and brain homogenate revealed a significant alteration in the JAK-mediated cytokine levels. MPTP administration also showed significant imbalance of inflammatory (increased TNF-α, IL-6 and NF-κb) versus anti-inflammatory cytokines (decreased IL-10 levels). MPTP-treated brain sections revealed alteration in the tissue architecture as well as undifferentiated bodies of varying contour and lesions. Chronic administration of CP690550 (3 and 10 mg/kg, po) for 7 days significantly reversed the behavioural, biochemical and histological alterations induced by MPTP. In conclusion, the findings of the present study govern the possible therapeutic potential of CP690550 in MPTP-treated mice and thus highlight the therapeutic potential of JAK inhibitors in treatment of Parkinson's disease.

Toxicity, preparation methods and applications of silver nanoparticles: an update.

Nanoparticles (range under 100 nm) prepared by different technology modes including physical, chemical, biological have many applications. Like in the same way silver nanoparticles are used for different beneficial actions like antimicrobial- antibacterial, antifungal and antiviral, anti-inflammatory, anticancer, water treatment, cosmetics, and in the textiles industry. As silver nanoparticles have shown wide application by different mechanisms against various pathophyisiological conditions. To maintain safety under their use, the study of the toxicity of silver nanoparticles has become more important. Health agencies like WHO, NIOSH, EPA, EFSA & EU have issued guidelines for unrisky exposure limit of silver nanopartricles in drinking water, food and breathing. The main purpose of this article is to summarize genotoxicity, cytotoxicity, neurotoxicity, reproductive toxicity of silver nanoparticles in both in vitro and in vivo studies focused on mechanism and methods of detection. The main mechanism of silver nanoparticles toxicity involves disruption of the mitochondrial respiratory chain, which results in the generation of ROS and the stoppage of ATP synthesis which further leads to a cascade of toxic events. ROS production measured by the technique like flow cytometry using DCFHDA dye and other method includes a confocal microscope, lipid peroxidation, etc. Different assay techniques used for evaluation of different kind of toxicities such as the comet assay, MTT assay, and histological assay, are also discussed.

Bioactive components to inhibit foam cell formation in atherosclerosis.

BACKGROUND: The production of lipid-laden cells in macrophages after significant ingestion of oxidized low-density lipoprotein is considered the most critical phase in the creation of atherosclerotic lesions, which is known as foam cell formation. Targeting foam cell development to find a potential therapeutic strategy for the management of atherosclerosis has yielded numerous promising outcomes. Multiple variables influence foam cell growth, including scavenger receptor expression, cholesterol transporter expression acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity. Plants used during herbal therapy have been shown to assist with a variety of ailments. RESULT: In this study, we found medicinal plants and their bioactive components suppress foam cell formation in a variety of ways; some inhibit cholesterol transporter and lectin-like oxidized low-density lipoprotein receptor-1 upregulation, while others inhibit the function of acyl CoA: cholesterol acyltransferase activity, and neutral cholesteryl ester hydrolase activity. CONCLUSION: Recent study findings related to the synthesis of the new active component from plant sources by focusing on the typical process involved in the generation of foam cells. We're also looking at using a cellular target-based therapeutic approach to generate novel plant-based medications for the cure of atherosclerosis.

Protective Impact of Edaravone Against ZnO NPs-induced Oxidative Stress in the Human Neuroblastoma SH-SY5Y Cell Line.

Extensive applications of ZnO NPs (zinc oxide nanoparticles) in daily life have created concern about their biotoxicity. Zinc oxide nanoparticles induce oxidative stress, inflammation, and apoptosis in neurons. Edaravone applies antioxidant agent and anti-inflammatory impacts in the different cells, as evaluated in both in vitro and in vivo experimental models. This study is designed to explore, how edaravone would avert mitochondrial impairment in human neuronal cells against ZnO NPs-induced toxicity. Accordingly, we analyzed here whether a pretreatment (for 24 h) with edaravone (10-100 µM) would enhance mitochondrial protection in the human neuroblastoma cells SH-SY5Y against ZnO NPs-induced toxicity. We found that edaravone at 25 µM averted the ZnO NPs-induced decrease in the amounts of adenosine triphosphate (ATP), just as on the activity of the complexes I and V. Also, edaravone induced an antioxidant activity by diminishing the levels of lipid peroxidation, protein carbonylation, and protein nitration in the mitochondrial membranes. Edaravone blocked the ZnO NPs-induced transcription factor nuclear factor-κB (NF-κB) upregulation. The inhibition of the heme oxygenase-1 (HO-1) enzyme by zinc protoporphyrin IX (ZnPP IX, 10 µM) smothered the preventive impacts brought about by edaravone with respect to mitochondrial function and inflammation. After this examination, it can be concluded that edaravone caused cytoprotective impacts in an HO-1-dependent manner in SH-SY5Y cells against ZnO NPs-induced toxicity.

Neurological repercussions of neonatal nicotine exposure: A review.

Smoking during pregnancy is hazardous to both the mother and the foetus, according to a substantial amount of recorded data. Exposure to nicotine and other compounds in cigarette smoke increases the risk of sudden infant death syndrome (SIDS) by two to five times during pregnancy. Serotonergic abnormalities have been discovered in SIDS infants in the zone of the medulla oblongata, which is known to control cardio-respiratory function. SIDS establishes a connection between depression, learning difficulties and behavioural disorders. Prenatal nicotine intake during the second trimester affects the dopaminergic neurological system, making the foetal brain more susceptible to nicotine and developing ADHD symptoms not just in a foetus but in adolescents also. Prenatal nicotine exposure alters the neurological route of neurotransmitters, acetylcholine and dopamine. Nicotine enhances neuronal activity in adults but desensitizes these processes in babies and young children exposed prenatally. The impact of a neurotoxin like nicotine is determined by the amount and duration of exposure. Continued exposure throughout pregnancy will influence a wide range of activities in the neurodevelopment, whereas exposure confined to a single stage of pregnancy may only affect the processes that are forming at that stage. To decrease the effect of nicotine on neonates due to maternal smoking strategies like nicotine replacement therapy (NRT), folic acid treatment and other behavioural treatments have been studied. Hence, this review focuses on the impact of exposure to nicotine on neonates, which results in various neurological consequences and smoking cessation therapies.