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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.)

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.

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.)

Copper (Cu), one of the essential transition metal acts as a prosthetic group for variety of proteins and metalloenzymes. However, it may be hazardous when administered in excess. Copper induced memory impairment and progression of neurodegenerative diseases have not yet been fully elucidated. The aim of the present study was to investigate the effect of exposure to copper sulphate (10mg/kg and 20mg/kg body weight, daily for 16 weeks) on brain copper concentration, few biochemical parameters indicative of oxidative stress and on different neurobehavioral functions in male Sprague Dawley rats. Copper-administered animals showed significant increase in brain copper concentration and a depleted Ceruloplasmin level. Different neurobehavioral studies revealed impaired memory and motor coordination in copper exposed rat. Spontaneous locomotors activity and depression symptoms were also noted in copper intoxicated rats. 8-hydroxy-2' -deoxyguanosine (8-OHdG) level, one of the predominant forms of free radical-induced oxidative lesions, and has been widely used as a biomarker for oxidative stress, increased in copper treated group. Copper induced oxidative stress in the brain was also evident from the increased lipid per oxidation (LPO) and nitrite level, depletion of reduced glutathione (GSH), and reduced activities of the antioxidant enzymes such as superoxide dismutase (SOD), and catalase. The present study thus suggests a significant correlation between copper induced oxidative stress and changes in neurobehavioral function in rats. The changes were more pronounced in animals exposed to a higher dose of copper (20mg/kg) than the lower dose.

Introduction: Arsenic and fluoride are recognized globally as the most serious inorganic contaminants in drinking water. As there is no safe and effective treatment for the cases of fluoride poisoning and combined arsenic-fluoride toxicity, the present study was planned to assess (i) the mechanism of combined exposure to arsenic and fluoride via biochemical and spectroscopic data; (ii) the effect of a thiol chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), either individually or in combination with the antioxidant vitamin C in reversing arsenic-fluoride toxicity; and (iii) whether combination therapy enhances arsenic and fluoride removal from blood and soft tissues., Methods: Rats were exposed to arsenic (50 mg l-1) and fluoride (50 mg l-1) individually and in combination for 9 months and later administered DMSA (50 mg kg-1) via an i.p. route and vitamin C (25 mg kg-1) orally for 5 days. Biochemical parameters suggestive of alterations in the heme synthesis pathway, oxidative stress in blood, the liver and the kidneys, and concentrations of arsenic and fluoride in blood and soft tissues were studied. We also studied the infrared (IR) spectra of DNA extracted from the livers and kidneys of the normal and exposed animals., Results: It was found that chronic arsenic and fluoride exposure led to an increased oxidative stress condition and impaired heme synthesis (67% inhibition in δ-aminolevulinic acid dehydratase activity and 38% increase in δ-aminolevulinic acid synthetase activity). The decreased antioxidant defense mechanism was marked by a 2.25 fold increased concentration of Reactive Oxygen Species (ROS) and a 28% decrease in the Glutathione (GSH) level. Interestingly, concomitant exposure to arsenic and fluoride did not lead to antagonistic effects as the toxic effects were the same as those seen during the individual exposure to both the toxicants. It suggests that toxicity depends on the dose and duration of exposure. Combination therapy with DMSA and vitamin C showed a better efficacy than monotherapy in terms of reducing the arsenic and fluoride burden (more than 70% in blood and soft tissues) as well as reversal in the altered biochemical variables indicative of oxidative stress and tissue damage (80-85%). The infrared (IR) spectra of DNA isolated from the liver and kidneys suggested that the treatment with vitamin C and DMSA had no beneficial effects in terms of reversing DNA damage., Conclusion: On the basis of the above observations, we suggest that the combinational therapy of DMSA and vitamin C would be more effective in arsenic and/or fluoride toxicity; however, more detailed studies are required to address recoveries in DNA damage.

Silver (Ag) and gold nanoparticles (Au NPs) have wide applications. They are increasingly being used in the medical devices, biosensors, cancer cell imaging, and cosmetics. Increased applications of these NPs in the technological advances have also led to the risk of exposure to these particles. This study investigated the toxic effects of Ag and Au NPs (1 μM and 2 μM, oral) on mouse erythrocytes and tissues after 14 consecutive days' exposure. Our results demonstrate significant increase in reactive oxygen species (ROS) and depletion of antioxidant enzyme status in erythrocytes and tissues. Hepatic and renal toxicity was evident from liver and kidney function tests. Inflammatory markers, interleukin-6 and nitric oxide synthase increased in plasma on administration following exposure to these NPs at both the doses. A more pronounced increase was noted in kidney metallothionein (MT) compared to liver MT on exposure to these NPs. Toxic potential of these NPs was further confirmed by increased 8-hydroxy-2'-deoxyguanosine levels in urine, a biomarker of DNA damage. Among the two NPs, Ag NP was more toxic at 2 μM dose compared to lower dose of 1 μM. The study suggests oxidative stress as the major mechanism responsible for the toxic manifestations induced by Ag and Au NPs., (© The Author(s) 2014.)

This study aimed to evaluate the protective efficacy of some antioxidants against sodium tungstate induced oxidative stress in male wistar rats. Animals were sub-chronically exposed to sodium tungstate (100ppm in drinking water) for three months except for control group. In the same time, many rats were supplemented orally with different antioxidants (alpha-lipoic acid (ALA), n-acetylcysteine (NAC), quercetin or naringenin (0.30mM)) for five consecutive days a week for the same mentioned period before. Exposure to sodium tungstate significantly (P<0.05) inhibit blood δ-aminolevulinic acid dehydratase (ALAD) activity, liver and blood reduced glutathione (GSH) levels and an increase in oxidized glutathione (GSSG) and thiobarbituric acid reactive species (TBARS) levels in tissues. ALA acid and NAC supplementation post sodium tungstate exposure increased GSH and also, was beneficial in the recovery of altered superoxide dismutase and catalase activity, besides, significantly reducing blood and tissue reactive oxygen species and TBARS levels. The results suggest a more pronounced efficacy of ALA acid and NAC supplementation than quercetin or naringenin supplementation post sodium tungstate exposure in preventing induced oxidative stress in rats., (Copyright © 2014 Elsevier GmbH. All rights reserved.)