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Saba Naqvi, Harish Sharma, Swaran JS Flora Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Lucknow 226002, IndiaCorrespondence: Swaran JS Flora; Saba NaqviDepartment of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-Raebareli), Bijnor-Sisendi Road, Lucknow, UP 226002, IndiaTel +91 9425482305; Tel +91 9411836483Email director@niperraebareli.edu.in; writetosaba@yahoo.comObjective: The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury.Methodology: Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50μg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues.Results: Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury.Conclusion: Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.Keywords: quercetin, ORMOSIL nanoparticles, cyclophosphamide, hepatoprotection, lactobionic acid

Byline: Manoj. Modi, Megha. Mittal, SJS. Flora Objective : The present study describes the effect of selenium either alone or in combination with meso-2, 3-dimercaptosuccinic acid (DMSA) against chronic arsenic [...]

Multiple sclerosis (MS) is a neuroimmunological disorder which causes axonal damage, demyelination and paralysis. Although numerous therapeutics have been developed for the effective treatment of MS and a few have been approved in recent decades, complete remission and treatment of MS remain a matter of concern. Nanotechnology is a potential approach for manipulating the properties of materials at the molecular level to attain desired properties. This approach is effective in the treatment of several CNS disorders by enhancing drug delivery, bioavailability and efficacy. We have briefly discussed the neuroimmunological disorders with a particular emphasis on MS. We also explored nanoengineered drug delivery systems, describing several nano-formulations for the treatment of MS, challenges and future of nanotechnology., (© 2024. The Author(s).)

Introduction: High incidence and fatality rates of cancer remain a global challenge. The success of conventional treatment modalities is being questioned on account of adverse effects. Photodynamic therapy (PDT) is a potential alternative. It utilizes a combination of photosensitizer (PS), light and oxygen to target the tissues locally, thereby minimizing the damage to neighboring healthy tissues. Conventional PSs suffer from poor selectivity, high hydrophobicity and sub-optimal yield of active radicals. Graphene nanomaterials (GNs) exhibit interesting particulate and photophysical properties in the context of their use in PDT., Area Covered: We focus on describing the mechanistic aspects of PDT-mediated elimination of cancer cells and the subsequent development of adaptive immunity. After covering up-to-date literature on the significant enhancement of PDT capability with GNs, we have discussed the probability of combining PDT with chemo-, immuno-, and photothermal therapy to make the treatment more effective., Expert Opinion: GNs can be synthesized in various size ranges, and their biocompatibility can be improved through surface functionalization and doping. These can be used as PS to generate ROS or conjugated with other PS molecules for treating deep-seated tumors. With increasing evidence on biosafety, such materials offer hope as antitumor therapeutics.

Neurological disorders (NDs) have a negative impact on the lives of individuals. There could be two explanations for this: unclear aetiology and lack of effective therapy. However, research in the past few years has revealed the role of bio-metals dyshomeostasis in NDs. The imbalance in copper (Cu) concentration may be one of the main causative factors in NDs. In this review, we have discussed the role of Cu in NDs, especially Alzheimer's disease (AD), including the molecular mechanisms involved in Cu-associated NDs like oxidative stress, neuroinflammation, and protein misfolding. We have also summarized the recent Cu-targeting approaches and highlighted the in vitro and in vivo studies recently being reported on the subject. Based on the earlier published reports, it could be speculated that the Cu targeting strategy might be an interesting and potential therapeutic approach for NDs. Various difficulties must be overcome to develop safe and efficient Cu-targeting medications for NDs., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by β-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fluoride (F) and arsenic (As) are two major contaminants of water and soil systems around the globe, causing potential toxicity to humans, plants, animals, and microbes. These contaminated soil systems can be restored by microorganisms that can tolerate toxic stress and provide rapid mineralization of soil, organic matter, and contaminants, using various tolerance mechanisms. Thus, the present study was undertaken with the arsenic hyper-tolerant bacterium Microbacterium paraoxydans strain IR-1 to determine its tolerance and toxicity to increasing doses of fluoride, either individually or in combination with arsenic, in terms of growth inhibition using a toxicity unit model. The minimum inhibitory concentration (MIC)and half maximal inhibitory concentration (IC 50 ) values for fluoride increased, from 9 g/L to 11 g/L and from 5.91 ± 0.1 g/L to 6.32 ± 0.028 g/L, respectively, in the combination (F + As) group. The statistical comparison of observed and expected additive toxicities, with respect to toxicity unit (TU difference), using Student's t -test, was found to be highly significant ( p < 0.001). This suggests the antagonistic effect of arsenic on fluoride toxicity to the strain IR-1. The unique stress tolerance of IR-1 ensures its survival as well as preponderance in fluoride and arsenic co-contaminated sites, thus paving the way for its possible application in the natural or artificial remediation of toxicant-exposed degraded soil systems.

Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chaurasia, Singh, Sur and Flora.)

Hospital effluents are loaded with drugs, radioactive elements, pathogens, etc. Effluents from treatment plants at source sites may get mixed up with potable water, leading to numerous detrimental/toxic effects. In this study, efforts were made to investigate the toxic effects of one such effluent from a local hospital on the reproductive characteristics of mice when orally administered daily for 60 consecutive days. We primarily focused on the changes in the morphology of the sperm and its geometric morphometrics, i.e., sperm head length and width, area, and perimeter, measured using ImageJ software. The incidence of sperm defects was recorded, and variations in the morphometrics were analyzed by one-way ANOVA using Tukey's post hoc test. A physico-chemical characterization of the water samples was also performed to assess the basic water quality. In summary, the study revealed the critical role of treated water in inducing different abnormalities in sperm, such as the absence of a head, bent necks, abnormal neck attachment, highly coiled tails, and missing tails. Significant differences ( p < 0.01 **, p < 0.001 ***) in the morphometrics of spermatozoa with banana heads, hammer heads, missing heads, pin heads, and missing hooks were noted compared to corresponding controls. It could thus be concluded that treated hospital effluent is still inadequately clean and contains significant amounts of toxicants that might be detrimental to sperm quality.

Copper (Cu) is an important trace element required for several biological processes. The use of copper is increasing gradually in several applications. Previous studies suggest that excess levels of copper are attributed to induce oxidative stress and inflammation, mediating tissue damage. Inline, melatonin the hormone of darkness has been reported to exhibit various therapeutic effects including strong free radical scavenging properties and anti-inflammatory effects. However, its effects against pulmonary injury promoted by copper are not explored and remain unclear so far. Therefore, the present study was aimed to investigate the protective effect of melatonin against copper-induced lung damage. Female Sprague Dawley (SD) rats were exposed to 250 ppm of copper in drinking water for 16 weeks and treated with melatonin (i.p.) 5 and 10 mg/kg from the week (13-16th). The extent of tissue damage was assessed by tissue oxidative stress parameters, metal estimation and histological analysis. Copper-challenged rats showed altered oxidative stress variables. In addition, metal analysis revealed increased copper accumulation in the lungs and histological staining results further indicated severe tissue injury and inflammatory cell infiltration in copper-exposed rats. To this side, treatment with melatonin showed antioxidant and anti-inflammatory activities evidenced by reduced oxidative stress, tissue inflammation and collagen deposition as compared to copper-exposed animals. Moreover, spectral findings suggested melatonin treatment modulated the frequency sift, as compared to copper-challenged animals. Altogether, the present results suggest that melatonin might play a potential role in preventing copper-induced lung aberrations via inhibiting the ROS-mediated oxidative stress and inflammation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Copper (Cu), being an essential trace metal, plays several roles in biological processes, though exposure to Cu can be potentially toxic to the brain and a few other soft organs. In the present study, we investigated the effects of the combined administration of monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), which is a new chelator, and alpha lipoic acid (ALA) and an antioxidant that is made naturally in the body and is also found in foods, against Cu-induced oxidative stress in rats. Rats were exposed to 20 mg/kg copper sulfate for 16 weeks once a day via the oral route. After 16 weeks of exposure, animals were divided into different sub-groups. Group I was divided into three subgroups: Group IA, control; Group IB, MiADMSA (75 mg/kg, oral); Group IC, ALA (75 mg/kg, oral), while Group II was divided into four subgroups: Group IIA, Cu pre-exposed; Group IIB, Cu+ MiADMSA; Group IIC, Cu+ ALA; Group IID, Cu+ ALA+ MiADMSA. Exposure to Cu led to significant neurobehavioral abnormalities; treatment with MiADMSA, and in particular MiADMSA + ALA, significantly ameliorated the neurobehavioral parameters and restored the memory deficits in rats. Oxidative stress variables (ROS, nitrite, TBARS, SOD, catalase) and inflammatory markers (TNF-α, and IL-1β), which were altered on Cu exposed rats, also responded favorably to ALA+ MiADMSA combined treatment. Thus, combined administration of MiADMSA and ALA might be a better treatment strategy than monotherapy with MiADMSA or ALA against Cu-induced neurotoxicity, particularly in reducing oxidative stress, neurobehavioral abnormalities, and inflammatory markers.

Tungsten (W) and its compounds have emerged as a relatively new area of environmental health concern in the last decade. Tungsten is environmentally benign due to its increasing use in armour-piercing munitions and as a replacement for lead in other ammunition. It has also been identified in various hazardous waste sites and therefore been proposed for inclusion in the Environmental Protection Agency National Priorities List. The major objective of this study was to evaluate the therapeutic efficacy of orally administered monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) against tungstate induced oxidative injury in blood, liver and kidneys of male Wistar rats. MiADMSA, a thiol chelator has gained wide recognition recently as a future chelating drug of choice specifically for arsenic and was chosen for this study as tungstate ions too have an affinity toward the -SH group thus, being less bioavailable in the body. We determined the effects of MiADMSA (50 mg/kg, p.o.) against sodium tungstate (500 ppm in drinking water, daily for 28 days) induced biochemical changes indicative of oxidative stress in blood, and other soft tissues of of male Wistar rats. Tungsten exposure led to an increased levels of Reactive Oxygen Species (ROS) in liver, kidney, spleen and blood accompanied also by an increase in TBARS levels. The GSH: GSSG ratio also showed a decrease on sodium tungstate intoxication. Treatment with MiADMSA restored most of the sodium tungstate-induced alterations in the biomarkers suggestive of oxidative stress. These preliminary results led us to conclude that sub-acute exposure to tungstate-induced oxidative stress could be effectively reduced by the administration of MiADMSA and thus might be a promising antidote for studying in detail its efficacy in reducing body tungstate burden and its excretion post tungstate exposure.

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.

Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.

Cancer is the second leading cause of death worldwide after cardiovascular disease. The major cause of high mortality is delayed detection. Therefore, detection at an early stage followed by early treatment can mitigate morbidity as well as mortality. The utilization of biomarker-based detection tools helps in early-stage recognition. Fortunately, biomarkers indicating disease status are released in to the circulation. These include traditional marker proteins as well as exosomes, micro-RNA (miRNA) and circulating tumor DNA (ct-DNA). Biosensors are biological and chemical reaction devices that generate signals based on analyte concentration. Due to analyte binding, these devices demonstrate high sensitivity and specificity. This review examines the use of surface plasmon resonance (SPR)-based sensors in the diagnosis of various cancer including those of the breast, prostate, lung, ovary, cervix and pancreas. SPR is a label-free, real-time and non-invasive optical biosensing technology representing a novel diagnostic tool in cancer detection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: To synthesize and evaluate the fused heterocyclic imidazo[1,2-a]pyridine based oxime as a reactivator against paraoxon inhibited acetylcholinesterase., Background: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon, which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation, or dermal. The current treatment regimen includes reactivator such as mono or bis-pyridinium oximes along with anticholinergic and anticonvulsant drugs that are recommended for the treatment of OP poisoning. Unfortunately, the drawback of the existing reactivator is the permanent charge present on the pyridinium, making them inefficient to cross the blood-brain barrier (BBB) and reactivate OP-inhibited central nervous system (CNS) acetylcholinesterase. Therefore, there is a need of a reactivator that could cross the BBB and reactivate the OP inhibited acetylcholinesterase., Objective: The objectives of the study were synthesis, molecular docking, BSA binding, and in-vitro estimation of oximes of various substituted imidazo [1,2-a]pyridine against paraoxon inhibited acetylcholinesterase., Methods: The reactivators were synthesized in three steps and characterized using various spectroscopic techniques. The molecular docking study was performed on 2WHP and 3ZLV PDB using the Glide-XP software. The acid dissociation constant (pKa) of oximes was calculated experimentally, and the drug-likeness properties of the oximes were calculated in silico using Molinspiration and Swiss ADME software. The binding of oximes with bovine serum albumin (BSA) was also investigated using a Fluorescence spectrophotometer. The reactivation potential of the oximes was determined by in vitro enzymatic assay., Results: The In-silico study inferred that the synthesized molecules fulfilled the parameters required for a successful CNS drug candidate. Furthermore, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. The binding of oximes with bovine serum albumin (BSA) revealed that there was a static quenching of intrinsic fluorescence of BSA by the oxime. The binding constant value and number of binding sites were found to be 0.24 x 10 4 mol -1 and 1, respectively., Conclusion: The results of the study concluded that this scaffold could be used for further designing of more efficient uncharged reactivators., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Recent studies have been reported emerging polymeric nanoparticles as a promising particulate carrier system for controlled and targeted drug delivery. Stimuli-responsive nanocarriers have shown characteristics, such as high drug uptake at specific sites or targeted cells with an advantage of no drug leakage. These stimuli-responsive polymeric systems are used to functionalize nanocarriers, such as dendrimers, metallic nanoparticles, polymeric nanoparticles, liposomal nanoparticles, and quantum dots., Objective: The study reviews the potential of smart stimuli-responsive carriers for therapeutic application and their behavior in external or internal stimuli, like pH, temperature, redox, light, and magnetic field. These stimuli- responsive drug delivery systems exhibit different drug release patterns in in vitro and in vivo studies. Stimuli- responsive nanocarriers are useful for both hydrophilic and hydrophobic drugs and release them on applied stimulus. This review highlights the recent development in the physical properties of polymeric materials and their application in stimuli-responsive specific drug delivery., Conclusion: The stimuli (smart, intelligent, programmable) drug delivery systems provide site-specific drug delivery with potential therapy for cancer, neurodegenerative, and lifestyle disorders. The stimuli-responsive- based nanocarriers are developing at a fast pace, and there is a huge demand for biocompatible and biodegradable responsive polymers for effective and safe delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Selenium is an essential mineral naturally found in soil, water, and some of the food and is required as essential elements in human and animal body. Se supplementation is required especially for those having Se deficiency. Food supplement of selenium has several forms such as selenocysteine, selenite, selenomethionine, and selenate. Recently, Se supplement as selenium nanoparticles (SeNPs) has gained worldwide attention due to its bioactivities and properties. In the present study, we determined the potential hepatotoxicity of nano and bulk selenium using low and high doses in mice. Twenty-five Swiss albino mice (n=5) were randomly divided into 5 groups and treated orally for 28 days: Group 1: sterile saline (0.9%) as a control; Group 2: sodium selenite (1mg/kg); Group 3: sodium selenite (4mg/kg); Group 4: selenium nanoparticles (1mg/kg); and Group 5: selenium nanoparticles (4mg/kg). Administration of nano-selenium (70-90 nm) led to an increase in the activities of serum transaminases (ALT and AST), while no significant effects were noted on biochemical variables indicative of changes in heme synthesis pathway and oxidative stress like blood δ-aminolevulinic acid dehydratase (δ-ALAD), hepatic reactive oxygen species (ROS), catalase activity, superoxide dismutase (SOD), malondialdehyde assay (MDA), reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) compared to controls, and a high dose of sodium selenite. Our results suggest that nano-selenium at low dose (1mg/kg) exhibited antioxidant effects in the liver compared to the high dose (4mg/kg) of SeNPs and sodium selenite (1 and 4 mg/kg). The data from the present study might be useful for pharmacologists and toxicologists in providing future directions while designing selenium-based therapeutic strategies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arsenic is a key environmental toxicant having significant impacts on human health. Millions of people in developing countries such as Bangladesh, Mexico, Taiwan, and India are affected by arsenic contamination through groundwater. Environmental contamination of arsenic leads to leads to various types of cancers, coronary and neurological ailments in human. There are several sources of arsenic exposure such as drinking water, diet, wood preservatives, smoking, air and cosmetics, while, drinking water is the most explored route. Inorganic arsenic exhibits higher levels of toxicity compared its organic forms. Exposure to inorganic arsenic is known to cause major neurological effects such as cytotoxicity, chromosomal aberration, damage to cellular DNA and genotoxicity. On the other hand, long-term exposure to arsenic may cause neurobehavioral effects in the juvenile stage, which may have detrimental effects in the later stages of life. Thus, it is important to understand the toxicology and underlying molecular mechanism of arsenic which will help to mitigate its detrimental effects. The present review focuses on the epidemiology, and the toxic mechanisms responsible for arsenic induced neurobehavioral diseases, including strategies for its management from water, community and household premises. The review also provides a critical analysis of epigenetic and transgenerational modifications, mitochondrial oxidative stress, molecular mechanisms of arsenic-induced oxidative stress, and neuronal dysfunction., Competing Interests: The authors declare no conflicts of interest.

Common symptoms such as dizziness, headache, olfactory dysfunction, nausea, vomiting, etc. in COVID-19 patients have indicated the involvement of the nervous system. However, the exact association of the nervous system with COVID-19 infection is still unclear. Thus, we have conducted a meta-analysis of clinical studies associated with neurological problems in COVID-19 patients. We have searched for electronic databases with MeSH terms, and the studies for analysis were selected based on inclusion and exclusion criteria and quality assessment. The Stats Direct (version 3) was used for the analysis. The pooled prevalence with 95% confidence interval of various neurological manifestations reported in the COVID-19 patients was found to be headache 14.6% (12.2-17.2), fatigue 33.6% (29.5-37.8), olfactory dysfunction 26.4% (21.8-31.3), gustatory dysfunction 27.2% (22.3-32.3), vomiting 6.7% (5.5-8.0), nausea 9.8% (8.1-11.7), dizziness 6.7% (4.7-9.1), myalgia 21.4% (18.8-24.1), seizure 4.05% (2.5-5.8), cerebrovascular diseases 9.9% (6.8-13.4), sleep disorders 14.9% (1.9-36.8), altered mental status 17.1% (12.3-22.5), neuralgia 2.4% (0.8-4.7), arthralgia 19.9% (15.3-25.0), encephalopathy 23.5% (14.3-34.1), encephalitis 0.6% (0.2-1.3), malaise 38.3% (24.7-52.9), confusion 14.2% (6.9-23.5), movement disorders 5.2% (1.7-10.4), and Guillain-Barre syndrome 6.9% (2.3-13.7). However, the heterogeneity among studies was found to be high. Various neurological manifestations related to the central nervous system (CNS) and peripheral nervous system (PNS) are associated with COVID-19 patients.

Organophosphorus (OP) compounds are typically a broad class of compounds that possess various uses such as insecticides, pesticides, etc. One of the most evil utilizations of these compounds is as chemical warfare agents, which pose a greater threat than biological weapons because of their ease of access. OP compounds are highly toxic compounds that cause irreversible inhibition of enzyme acetylcholinesterase, which is essential for hydrolysis of neurotransmitter acetylcholine, leading to series of neurological disorders and even death. Due to the extensive use of these organophosphorus compounds in agriculture, there is an increase in the environmental burden of these toxic chemicals, with severe environmental consequences. Hence, the rapid and sensitive, selective, real-time detection of OP compounds is very much required in terms of environmental protection, health, and survival. Several techniques have been developed over a few decades to easily detect them, but still, numerous challenges and problems remain to be solved. Major advancement has been observed in the development of sensors using the spectroscopic technique over recent years because of the advantages offered over other techniques, which we focus on in the presented review., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Ferroptosis is a newly identified regulated form of cell death, which is thought to play a major role in neurodegenerative diseases. In this review, we discuss recent studies elucidating the molecular mechanisms involved in the regulation and execution of ferroptotic cell death and also its role in the brain. Ferroptosis is regulated mainly via iron homeostasis, glutathione metabolism, and lipid peroxidation. Ferroptotic cell death and pro-ferroptotic factors are correlated with the etiopathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). Ferroptosis and etiological factors act synergistically in PD and AD pathogenesis. Furthermore, several preclinical and clinical studies targeting ferroptosis in PD and AD have also shown positive results. Evidence of ferroptosis in the brain thus gives new insights into understanding neurodegenerative diseases. Ferroptosis studies in the brain are still in their infancy, but the existing pieces of evidence suggest a strong correlation between ferroptotic cell death and neurodegenerative diseases. Thus, ferroptosis might be a promising target for treating neurodegenerative diseases., (© 2021 Wiley Periodicals LLC.)

Neurodegenerative disorders can arise as a result of amyloid-β production and misfolding of its protein. The complex anatomy of the brain and the unresolved mechanics of the central nervous system hinder drug delivery; the brain is sheathed in a highly protective blood-brain barrier, a tightly packed layer of endothelial cells that restrict the entry of certain substances into the brain. Nanotechnology has achieved success in delivery to the brain, with preclinical assessments showing an acceptable concentration of active drugs in the therapeutic range, and nanoparticles can be fabricated to inhibit amyloid and enhance the delivery of the therapeutic molecule. This review focuses on the interactions of nanoparticles with amyloid-β aggregates and provides an assessment of their theranostic potential., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1β, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Deore, S, Naqvi, Kumar and Flora.)

Ferroptosis is a recently recognized regulated form of cell death characterized by accumulation of lipid-based reactive oxygen species (ROS), particularly lipid hydroperoxides and loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4). This iron-dependent form of cell death is morphologically, biochemically, and also genetically discrete from other regulated cell death processes, which include autophagy, apoptosis, necrosis, and necroptosis. Ferroptosis is defined by three hallmarks, defined as the loss of lipid peroxide repair capacity by GPX4, the bioavailability of redox-active iron, and oxidation of polyunsaturated fatty acid- (PUFA-) containing phospholipids. Experimentally, it can be induced by many compounds (e.g., erastin, Ras-selective lethal small-molecule 3, and buthionine sulfoximine) and also can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and deferoxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin and liproxstatin). The sensitivity of a cell towards ferroptotic cell death is tightly associated with the metabolism of amino acid, iron, and polyunsaturated fatty acid metabolism, and also with the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis sensitivity is also governed by many regulatory proteins, which also link ferroptosis to the function of key tumour suppressor pathways. In this review, we highlight the discovery of ferroptosis, the mechanism of ferroptosis regulation, and its association with other cellular metabolic processes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ankita Sharma and Swaran Jeet Singh Flora.)

Clean and safe water is a fundamental human need for multi-faceted development of society and a thriving economy. Brisk rises in populations, expanding industrialization, urbanization and extensive agriculture practices have resulted in the generation of wastewater which have not only made the water dirty or polluted, but also deadly. Millions of people die every year due to diseases communicated through consumption of water contaminated by deleterious pathogens. Although various methods for wastewater treatment have been explored in the last few decades but their use is restrained by many limitations including use of chemicals, formation of disinfection by-products (DBPs), time consumption and expensiveness. Nanotechnology, manipulation of matter at a molecular or an atomic level to craft new structures, devices and systems having superior electronic, optical, magnetic, conductive and mechanical properties, is emerging as a promising technology, which has demonstrated remarkable feats in various fields including wastewater treatment. Nanomaterials encompass a high surface to volume ratio, a high sensitivity and reactivity, a high adsorption capacity, and ease of functionalization which makes them suitable for application in wastewater treatment. In this article we have reviewed the techniques being developed for wastewater treatment using nanotechnology based on adsorption and biosorption, nanofiltration, photocatalysis, disinfection and sensing technology. Furthermore, this review also highlights the fate of the nanomaterials in wastewater treatment as well as risks associated with their use.

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a lipophilic chelator has been evaluated for its potential use as an antidote in arsenic poisoning. The pharmacokinetics and pharmacodynamics properties of a drug could be understood via study its mechanism of interaction with bovine serum albumin protein (BSA). Therefore, the interaction between MiADMSA with BSA was investigated using various spectroscopic techniques and computational methods. Linear quenching of BSA intrinsic fluorescence intensity with the increasing concentration of MiADMSA was observed in the fluorescence study. Furthermore, synchronous results revealed that MiADMSA slightly changed the conformation of BSA. The binding constant value of the BSA-MiADMSA complex was found 1.60 × 10 4  M -1 at 298 K. The value of thermodynamic parameters ΔG, ΔH, and ΔS described that the process is spontaneous, endothermic, and hydrophobic forces are involved in the interaction of MiADMSA with BSA. Competitive site marker experiments showed that MiADMSA binds to site-II of BSA. Conformational changes of BSA with the interaction of MiADMSA were apparent by CD, UV-Visible, FT-IR, and 3D fluorescence spectroscopy. To strengthen the experimental findings we have also performed a theoretical study on the BSA-MiADMSA complex. Two sites were identified with docking score of - 6.642 kcal/mol at site II a and - 3.80 kcal/mol for site II b via molecular docking study. Molecular dynamics simulation study inferred the stability of the BSA-MiADMSA complex which was analyzed in a long simulation run. The experimental and computational studies have shown the effective binding of MiADMSA with BSA which is essential for the transportation and elimination of a drug from the body.

Three-dimensional (3D) printing is gaining numerous advances in manufacturing approaches both at macro- and nanoscales. Three-dimensional printing is being explored for various biomedical applications and fabrication of nanomedicines using additive manufacturing techniques, and shows promising potential in fulfilling the need for patient-centric personalized treatment. Initial reports attributed this to availability of novel natural biomaterials and precisely engineered polymeric materials, which could be fabricated into exclusive 3D printed nanomaterials for various biomedical applications as nanomedicines. Nanomedicine is defined as the application of nanotechnology in designing nanomaterials for different medicinal applications, including diagnosis, treatment, monitoring, prevention, and control of diseases. Nanomedicine is also showing great impact in the design and development of precision medicine. In contrast to the "one-size-fits-all" criterion of the conventional medicine system, personalized or precision medicines consider the differences in various traits, including pharmacokinetics and genetics of different patients, which have shown improved results over conventional treatment. In the last few years, much literature has been published on the application of 3D printing for the fabrication of nanomedicine. This article deals with progress made in the development and design of tailor-made nanomedicine using 3D printing technology.

New chemical agents that could combat increasing antibiotic resistance are urgently needed. In this mini-review, an old but highly relevant RNA sequence which is crucial for the continuation of bacterial life-cycle is covered. Some of the most significant advances of the last decade in sensing and targeting the bacterial rRNA A-site: a well-validated binding site of proverbially known aminoglycoside antibiotics are described. Some of the major advances in direct sensing of the bacterial decoding side (A-site) are described and also new fluorescent molecules that are capable of detecting lead compounds through high-throughput assays by displacement of fluorescent probe molecules are highlighted. Lastly, some of the recently discovered non-aminoglycoside small molecule binders of bacterial rRNA A-site as a new class of molecules that could provide future scaffolds and molecules for developing new antibacterial agents have been discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nanodiamonds (ND) belong to the nano-carbon family, which involves several synthesis, post-synthesis methods, and other modifications for ND preparation. NDs have played vital role both inside and outside of medicine in recent years. The study of NDs has stated in early 1960s, NDs are smaller particles with a size of about 4-5 nm with confined size distribution, large-scale synthesis at lower costs relying on the carbon explosives ignition, apparent surface functional design along with bio-conjugation and extreme biocompatibility. It has been predicted that the ND's magnetic characteristics will contribute to the up-growth of various therapeutic promoters for delivery vehicles, diagnostic probes, gene therapy, tissue scaffolds, anti-bacterial and anti-viral treatments, and devices like nano-robots. Furthermore, the wide applications of biotechnology have displayed the potential usage of NDs in certain bioanalytical needs like fluorescent bio labeling through fluorescent and protein purification of proteins. In this current review, the determination of ND's design, property, classes, constancy, organization, surface modification, biocompatibility, and its applications in the biomedical field have penned. The usage of ND as anti-neoplastic agents and in other health related formulations have displayed exceptional results for future growth. Additionally, NDs provide other functionalities such as production of biodegradable surgical devices of bone, the assassination of drug resistant microbes and viruses, tissue engineering scaffolds, and aids in the delivery of genetic matter into the nucleus of cells.

Despite the availability of sufficient data on the effects of individual metal exposure on living organisms, a critical knowledge gap still exists in predicting effects of multi-metals particularly on the pituitary-testicular axis. Thus, the aim of the present study was to check the effects of individual or combined (binary and ternary) exposure to aluminum, copper, and zinc on (i) sperm and testosterone levels (ii) oxidative stress and (iii) structural changes in testis of male Wistar rats. Animals were exposed to aluminum, copper, and zinc either individually (20   mg/kg, orally, once, daily), binary (10   mg/kg each, orally, once daily) or in ternary combination (5   mg/kg, each, orally, once daily) for 24   weeks. The exposure to aluminum, copper individually and in combination led to a significant decrease in sperm counts and an increased oxidative stress compared to the control group. Exposure to zinc caused significant decrease in oxidative stress and an increase in different sperm variables. The exposure to zinc with aluminum or copper had no toxic effects on testis while concomitant exposure to aluminum, copper, and zinc produced more pronounced testicular injury. In summary, while co-exposure to zinc with aluminum or copper produced reproductive toxicity the co-exposure to all the three metals may lead to a significant testicular toxicity and these changes were related to increase in oxidative stress in rats.

Purpose: In this study, a novel D-α-tocopheryl polyethylene glycol succinate (TPGS) modified bovine serum albumin (BSA) nanoparticles (NPs) were developed for delivery of Anastrozole (ANZ) which is optimized by Box-Behnken design (BBD). Fabricated TPGS-ANZ-BSA NPs were evaluated for their physicochemical and drug release characteristics., Methods: TPGS-ANZ-BSA NPs were prepared by desolvation thermal gelation method and the effects of critical process parameter (CPP) which are BSA amount, TPGS concentration and stirring speed on the critical quality attributes (CQA) such as % drug loading (%DL) and particle size were studied using BBD. TPGS-ANZ-BSA NPs were characterized using different spectroscopic techniques including UV-Visible and FTIR is used to confirm the entrapment of ANZ in BSA. DSC and PXRD revealed the amorphization of ANZ in the TPGS-ANZ-BSA NPs after freeze drying. Scanning electron microscopy (SEM) analysis was performed for the surface morphology analyses NPs. In vitro release studies were performed at pH 5.5 and pH 7.4 for 48h to mimic tumour microenvironment., Results: The BBD optimized TPGS-ANZ-BSA NPs showed 107 nm particle size with %DL 8.5± 0.5%. The spectroscopic and thermal characterizations revealed the successful encapsulation of ANZ inside the NPs. The TPGS-ANZ-BSA NPs were found to exhibit burst release at pH 5.5 and sustained release at pH 7.4. The short-term stability displayed no significant changes in physical properties TPGS-ANZ-BSA NPs at room temperature for a period one month., Conclusion: The BBD optimized TPGS-ANZ-BSA nanoparticles showed enhanced physiochemical properties for ANZ and potential candidates for anticancer agent drugs delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Highly stable pine oil-loaded nanoemulsions were evaluated for nutraceutical and storage stability applications. Pine oil-loaded nanoemulsion preparation was done with pine oil as the oily phase and additionally with different ratios of the non-ionic surfactant (Tween 80) and cosurfactant (ethanol) in an aqueous solution using the isothermal low-energy or spontaneous emulsification method. A transparent and stable nanoemulsion was obtained with a combination of pine oil (5 wt %), surfactant mixture (35 wt %), and water quantity sufficient (qs) by the isothermal low-energy method. The mean droplet size and ζ-potential of the fabricated nanoemulsion were ≈14 nm and -3.4 mV, respectively. The size of the transparent nanoemulsion increased to ∼45 nm and showed turbidity at 60 °C. Microrheological investigation highlighted the gel-sol-gel conversion in the presence of applied angular frequency at 25 °C. The loss modulus shifted to lower frequency at 60 °C in comparison to other temperatures. The anticholinesterase (AChE) inhibition activity of the pine oil-loaded nanoemulsion suggested a possible therapeutic value, and at 0.10% concentration of the nanoemulsion, the AChE inhibition activity was ≈95.72 ± 5.59%. These studies have important implications in fabrication and optimization of a nanoemulsion as a delivery system for combating reminiscence in Alzheimer's disease and application in the nutraceutical-based industry. This isothermal low-energy method offers an advantage of preparing an edible oil delivery system using simple and rapid operational parameters., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Chelation therapy is considered as a safe and effective strategy to combat metal poisoning. Arsenic is known to cause neurological dysfunctions such as impaired memory, encephalopathy, and peripheral neuropathy as it easily crosses the blood-brain barrier. Oxidative stress is one of the mechanisms suggested for arsenic-induced neurotoxicity. We prepared Solid Lipid nanoparticles loaded with Monoisoamyl 2, 3-dimercaptosuccinic acid (Nano-MiADMSA), and compared their efficacy with bulk MiADMSA for treating arsenic-induced neurological and other biochemical effects. Solid lipid nanoparticles entrapping MiADMSA were synthesized and particle characterization was carried out by transmission electron microscopy (TEM) and dynamic light scattering (DLS). An in vivo study was planned to investigate the therapeutic efficacy of MiADMSA-encapsulated solid lipid nanoparticles (Nano-MiADMSA; 50 mg/kg orally for 5 days) and compared it with bulk MiADMSA against sodium meta-arsenite exposed rats (25 ppm in drinking water, for 12 weeks) in male rats. The results suggested the size of Nano-MiADMSA was between 100-120 nm ranges. We noted enhanced chelating properties of Nano-MiADMSA compared with bulk MiADMSA as evident by the reversal of oxidative stress variables like blood δ-aminolevulinic acid dehydratase (δ-ALAD), Reactive Oxygen Species (ROS), Catalase activity, Superoxide Dismutase (SOD), Thiobarbituric Acid Reactive Substances (TBARS), Reduced Glutathione (GSH) and Oxidized Glutathione (GSSG), Glutathione Peroxidase (GPx), Glutathione-S-transferase (GST) and efficient removal of arsenic from the blood and tissues. Recoveries in neurobehavioral parameters further confirmed nano-MiADMSA to be more effective than bulk MiADMSA. We conclude that treatment with Nano-MiADMSA is a better therapeutic strategy than bulk MiADMSA in reducing the effects of arsenic-induced oxidative stress and associated neurobehavioral changes., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Wilson disease (WD) is an autosomal-recessive disorder associated with the impaired copper metabolism, resulting in hepatic and neurologic manifestations. D-Pencillamine (DPA) is a first-line of treatment however, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA), is gaining recognition recently as a future chelating agent of choice. We evaluated the effects of MiADMSA against copper-induced (20 mg/kg, orally, once, daily for 16 weeks) hepatic and immunological changes in the male Sprague Dawley (SD) rats. Copper overload increased the levels of pro-oxidant and concurrently decreased the levels of antioxidant enzymes in the liver. Increased oxidative stress triggered the up-regulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in the liver and down-regulated the anti-inflammatory cytokine IL-4. Altered liver function parameters as well as serum immunoglobulins' (IgG, IgA, IgE, and IgM) levels, were also noted. MiADMSA treatment restored most of copper altered biochemical and immunological changes. Further, the histopathological changes proved that MiADMSA treatment ameliorated copper induced hepatic injury. Infra red spectra of liver tissue indicated shift in the characteristic -OH peak during copper exposure while the shifting came to normal in MiADMSA administered rat liver. We conclude that MiADMSA could be a promising antidote for the chronic copper toxicity and possibly in the clinical management of WD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: copper dyshomeostasis has long been linked with several neurodegenerative disorders. The binding of Cu with amyloid beta and other neuronal proteins in the brain leads to the generation of oxidative stress, which eventually causes neurotoxicity., Method: the present study was aimed at elucidating the efficacy of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) and d-penicillamine (DPA) (0.3 mEq kg-1, oral administration for 2 weeks) against Cu(ii)-induced (20 mg kg-1, oral administration for 16 weeks) neurotoxicity in Sprague-Dawley (SD) rats., Results: we observed that the MiADMSA treatment modulated the altered oxidative and nitrosative stress parameters, antioxidant enzymes, and acetylcholinesterase (AChE) activity. Significant improvements were noticed in the neurobehavioral parameters except for the memory parameter. We also observed moderate improvement of memory impairment in the rats treated with MiADMSA and DPA post Cu(ii) exposure, as assessed by a passive avoidance test. Disease progression involves multiple factors and results in the up-regulation of intra and extracellular proteins such as amyloid beta and tau proteins; the expressions of these proteins were significantly reduced by the treatment proposed in our study, and these results were confirmed by ELISA and qRT-PCR. The expression of caspase-3 was higher in Cu(ii)-exposed rats, whereas it was lower in the MiADMSA-treated group. The proposed treatment reduced the copper-induced histological changes in the cortex and hippocampus regions of the brain., Conclusion: it can be summarised from the present study that MiADMSA is effective in reducing Cu(ii)-induced oxido-nitrosative stress, antioxidant defense enzymes, neurobehavioral changes, neuronal markers, apoptotic markers, and their genetic expressions. We conclude that chelation therapy using MiADMSA might be a promising approach for the treatment of copper-induced neurotoxicity.

Background and Purpose: Arsenicosis is a major threat to public health and is a major cause of the development of urinary bladder cancer. Oxidative/ nitrosative stress is one of the key factors for these effects but the involvement of other associated factors is less known. There is a lack of data for the efficacy of chelator against urinary bladder carcinogenesis. The present study demonstrates the early signs of arsenic exposed urinary bladder carcinogenesis and its attenuation by Monoisoamyl dimercaptosuccinic acid (MiADMSA)., Methods: Male rats were exposed to 50 ppm of sodium arsenite and dimethylarsinic acid (DMA) via drinking water for 18 weeks and treated with MiADMSA (50 mg/kg, orally once daily for 5 days) for 3 weeks with a gap one week between the two courses of treatments. We compared in vivo data with in vitro by co-exposing 100 nM of sodium arsenite and DMA to rat (NBT-II) as well as human transitional epithelial carcinoma (T-24) cells with 100 nM of MiADMSA., Results: The data showed that sodium arsenite and DMA exposure significantly increased the tissue arsenic contents, ROS, TBARS levels, catalase, SOD activities and significantly decreased GSH level which might be responsible for an increased 8-OHdG level. These changes might have increased pro-oncogenic biomarkers like MMP-9 and survivin in serum, bladder tissues, NBT-II, and T-24 cells. High cell migration and clonogenic potential in NBT-II and T-24 cells exposed to arsenic suggest pronounced carcinogenic potential. Significant recovery in these biomarkers was noted on treatment with MiADMSA., Conclusion: Early signs of urinary bladder carcinogenesis were observed in arsenic and DMA exposed rats which were linked to metal accumulation, oxidative/ nitrosative stress, 8-OHdG, MMP-9 and survivin which were reduced by MiADMSA possibly via its efficient chelation abilities in vivo and in vitro., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)