Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases.

Neurological disorders incidences are increasing drastically due to complex pathophysiology, and the nonavailability of disease-modifying agents. Several attempts have been made to identify new potential chemicals to combat these neurological abnormalities. At present, complete abolishment of neurological diseases is not attainable except for symptomatic relief. However, dietary recommendations to help brain development or improvement have increased over the years. In recent times, cruciferous vegetables and their phytochemicals have been identified from preclinical and clinical investigations as potential neuroprotective agents. The present review highlights the beneficial effects and molecular mechanisms of phytochemicals such as indole-3-carbinol, diindolylmethane, sulforaphane, kaempferol, selenium, lutein, zeaxanthin, and vitamins of cruciferous vegetables against neurological diseases including Parkinson's disease, Alzheimer's disease, stroke, Huntington's disease, autism spectra disorders, anxiety, depression, and pain. Most of these cruciferous phytochemicals protect the brain by eliciting antioxidant, anti-inflammatory, and antiapoptotic properties. Regular dietary intake of cruciferous vegetables may benefit the prevention and treatment of neurological diseases. The present review suggests that there is a lacuna in identifying the clinical efficacy of these phytochemicals. Therefore, high-quality future studies should firmly establish the efficacy of the above-mentioned cruciferous phytochemicals in clinical settings.

Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents.

Coumarin-based different series of hydrazone derivatives were synthesized and evaluated for anticancer activity against four different human cancer cell lines. The activity of the compounds were compared with doxorubicin as a standard drug and all the compounds exhibited good to moderate cytotoxicity with IC50 values ranging from 6.07 to 60.45 µM against all the examined cancer cell lines. Based on the screening results, it was concluded that the compounds 12a and 18a were the most promising medicinal entities. In vitro tubulin polymerisation inhibition assay was performed for the compounds 12a and 18a and these two compounds displayed good potency when compared with colchicine as the standard drug. The interaction of these compounds with tubulin protein was also studied with the help of molecular docking technique using Discovery studio software. Furthermore, the molecular and ADMET properties of the compounds were computed with Osiris property software and PreADMET server. The compounds exhibited exciting in vitro and in silico results. Hence we propose that the compounds 12a and 18a could be developed as tubulin targeted potential antiproliferative agents.

Synthesis and biological evaluation of novel 4,7-dihydroxycoumarin derivatives as anticancer agents.

A series of novel 4,7-dihydroxycoumarin based acryloylcyanohydrazone derivatives were synthesized and evaluated for antiproliferative activity against four different cancer cell lines (A549, HeLa, SKNSH, and MCF7). Most of the compounds displayed potent cytotoxicity with IC50 values ranging from 3.42 to 31.28 µM against all the tested cancer cell lines. The most active compound, 8h was evaluated for pharmacological mechanistic studies on cell cycle progression and tubulin polymerization inhibition assay. The results revealed that the compound 8h induced the cell cycle arrest at G2/M phase and inhibited tubulin polymerization with IC50 = 6.19 µM. Experimental data of the tubulin polymerization inhibition assay was validated by molecular docking technique and the results exhibited strong hydrogen bonding interactions with amino acids (ASN-101, TYR-224, ASN-228, LYS-254) of tubulin.

Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective.

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose-dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose-dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.

In vitro genotoxicity assessment of nickel(II) oxide nanoparticles on lymphocytes of human peripheral blood.

The current study was intended to elucidate the cytotoxicity, genotoxicity ability of nickel oxide (NiO) nanoparticles (NPs) and assessment of preliminary mechanism of the toxicity. Characterization studies showed that NiO-NPs have a particle size of 17.94 (±3.48) nm. The particle size of the NPs obtained by dynamic light scattering method in Milli-Q and RPMI 1640 media was 189.9 (±17.1) and 285.9 (±19.6) nm, respectively. The IC50 concentration for NiO-NPs after 24 hours of treatment was estimated as 23.58 µg/mL. Comet and cytokinesis-block micronucleus assays revealed a significant dose- and time-dependent genotoxic potential of NiO-NPs. Morphological assessment of the lymphocytes upon exposure to NiO-NPs showed that the mechanism of toxicity was apoptosis. Reactive oxygen species analysis and lipid peroxidation patterns were aligned with the cytotoxicity and genotoxicity endpoints. Thus, the preliminary mechanism of NiO-NPs for cytotoxicity on lymphocytes was assumed to be oxidative stress-mediated apoptosis and DNA damage. Furthermore, these NiO-NPs are considered a potentially hazardous substance at environmentally significant levels. Further investigations are suggested to understand the immunotoxic effects of NiO-NPs.

Allium cepa root tip assay in assessment of toxicity of magnesium oxide nanoparticles and microparticles.

Allium cepa bioassay had been used from decades for the assessment of toxicants and their harmful effects on environment as well as human health. Magnesium oxide (MgO) particles are being utilized in different fields. However, reports on the adverse effects of MgO nanoparticles on the environment and mankind are scarce. Hence, the toxicity of MgO particles is of concern because of their increased utilization. In the current study, A. cepa was used as an indicator to assess the toxicological efficiency of MgO nano- and microparticles (NPs and MPs) at a range of exposure concentrations (12.5, 25, 50, and 100µg/mL). The toxicity was evaluated by using various bioassays on A. cepa root tip cells such as comet assay, oxidative stress and their uptake/internalization profile. Results indicated a dose dependent increase in chromosomal aberrations and decrease in mitotic index (MI) when compared to control cells and the effect was more significant for NPs than MPs (at p<0.05). Comet analysis revealed that the Deoxyribonucleic acid (DNA) damage in terms of percent tail DNA ranged from 6.8-30.1 over 12.5-100µg/mL concentrations of MgO NPs and was found to be significant at the exposed concentrations. A significant increase in generation of hydrogen peroxide and superoxide radicals was observed in accordance with the lipid peroxidation profile in both MgO NPs and MPs treated plants when compared with control. In conclusion, this investigation revealed that MgO NPs exposure exhibited greater toxicity on A. cepa than MPs.

Iodine mediated pyrazolo-quinoline derivatives as potent anti-proliferative agents.

A novel series of substituted pyrazolo-quinoline derivatives 7pa-7qg were synthesized efficiently by using molecular iodine in DMSO and further characterized based on 1H NMR, 13C NMR, IR and HRMS spectral studies. All the synthesized derivatives were screened for their in vitro cytotoxic activity against a panel of five different cancer cell lines such as A549, HeLa, SKNSH, HepG2 and MCF7. The compounds 7pc, 7pd, and 7pj exhibited considerable to promising anti-proliferative activity with IC50 values of 3.76, 3.87 and 3.83 µM against SKNSH cancer cell line. It was revealed that the compounds 7pa and 7pg have shown very close IC50 values of 2.43 and 6.01 µM, against A549 and MCF7 cancer cell lines respectively, which compared to positive control of Doxorubicin. This is the first report on the synthesis and in vitro anti-proliferative evaluation of pyrazolo-quinoline derivatives.

Genotoxicity, biochemical, and biodistribution studies of magnesium oxide nano and microparticles in albino wistar rats after 28-day repeated oral exposure.

Increased utilization and exposure levels of Magnesium oxide (MgO) nanoparticles (NPs) to humans and environment may raise unexpected consequences. The goal of this study was to evaluate the toxicological implications of MgO NPs and MPs after 28 day repeated oral administration in Wistar rats with three different doses (250, 500, and 1000 mg/kg). The MgO particles were characterised systematically in order to get more insights of the toxicological behaviour. MgO NPs induced significant DNA damage and aberrations in chromosomes. Moreover, hepatic enzymes released into the systemic circulation caused significant elevated levels of physiological enzymes in blood. NPs could interfere with proteins and enzymes and alter the redox balance in cell environment. Significant accumulation of Mg in all tissues and clearance via urine and faeces was noted in size dependent kinetics. Oral administration of MgO NPs altered the biochemical and genotoxic parameters in dose dependent and gender independent manner.

Biochemical alterations induced by nickel oxide nanoparticles in female Wistar albino rats after acute oral exposure.

CONTEXT: Nickel oxide (NiO) nanoparticles (NPs) with appropriate surface chemistry have been widely used for their potential new applications in biomedical industry. Increased usage of these NPs enhances the chance of exposure of personnel involved in the work place. OBJECTIVE: This study was designed to assess the ability of NiO NPs to cause biochemical alterations post-acute oral exposure in female Wistar rats. MATERIALS AND METHODS: Rats were administered with 125, 250, and 500 mg/kg doses of NiO NPs for haematological, biochemical, and histopathological studies. Biodistribution patterns of NiO NPs in female Wistar rats were also monitored. RESULTS: NiO NPs caused significant (p < 0.01) inhibition of RBC and brain AchE of treated rats at the high dose. Activation of the hepatotoxicity marker enzymes, aminotransferases, was recorded in serum and liver, whereas inhibition was observed in kidney. The activity of antioxidant enzymes was also altered by NiO NPs in a dose-dependent manner and found to be significant at the high dose of exposure. CONCLUSIONS: This study revealed that exposure to nanosized NiO particles at acute doses may cause adverse changes in animal biochemical profiles. Further, the in vivo studies on toxicity evaluation help in biomonitoring of the potential contaminants.

Acute oral toxicity study of magnesium oxide nanoparticles and microparticles in female albino Wistar rats.

Advancements in nanotechnology have led to the development of the nanomedicine, which involves nanodevices for diagnostic and therapeutic purposes. A key requirement for the successful use of the nanoparticles (NPs) in biomedical applications is their good dispensability, colloidal stability in biological media, internalization efficiency, and low toxicity. Therefore, toxicological profiling is necessary to understand the mechanism of NPs and microparticles (MPs). MgO NPs have attracted wide scientific interest due to ease of synthesis, chemical stability and unique properties. However, their toxic effects on humans should also be of concern with the increased applications of nano MgO. The present study was aimed to assess the toxicological potential of MgO NPs in comparison to their micron counterparts in female Wistar rats. Toxicity was evaluated using genotoxicity, histological, biochemical, antioxidant and biodistribution parameters post administration of MgO particles to rats through oral route. The results obtained from the investigation revealed that the acute exposure to the high doses of MgO NPs produced significant (p < 0.01) DNA damage and biochemical alterations. Antioxidant assays revealed prominent oxidative stress at the high dose level for both the particles. Toxicokinetic analysis showed significant levels of Mg accumulation in the liver and kidney tissues apart from urine and feces. Further, mechanistic investigational reports are warranted to document safe exposure levels and health implications post exposure to high levels of NPs.

Toxicological assessment of tungsten oxide nanoparticles in rats after acute oral exposure.

Advances in and the rapid growth of the nanotechnology sector have escalated manufacture of nanoparticles (NPs), resulting in a significant increase in the probability of exposure of humans and wildlife to these materials. Many NPs have been found to exert genotoxicity. Therefore, genotoxicity studies are mandatory to assess the toxicity of NPs as a concern of succumbing to genetic diseases and cancers are universal. Tungsten oxide (WO3) NPs are being explored extensively in various fields. However, the toxicological data of WO3 NPs by oral route in mammals is limited. Hence, the goal of the current investigation was to evaluate the acute toxicity of WO3 NPs and microparticles (MPs) after single oral administration with 100, 500 and 1000 mg/kg body weight doses in female Wistar rats. TEM, dynamic light scattering and laser Doppler velocimetry techniques were used to characterise the particles. The genotoxicity studies were conducted using comet, micronucleus and chromosomal aberration assays. Alterations in biochemical indices and metal distribution in various organs were also evaluated. The mean size of WO3 NPs and MPs by TEM was 53.2 ± 1.91 nm and 5.17 ± 3.18 µm, respectively. The results revealed a significant increase in DNA damage and micronuclei and chromosomal aberrations after exposure to 1000 mg/kg dose of WO3 NPs. Significant alterations in aspartate transaminase, alanine transaminase, reduced glutathione, catalase and malondialdehyde levels in serum and liver were found only at the higher dose of WO3 NPs. Tungsten (W) biodistribution was observed in all the tissues in a dose-, time- and organ-dependent manner. In addition, the maximum concentration of W was found in the liver and the least in the brain was observed. The test substances were found to have a relatively low acute toxicity hazard. The data obtained gives preliminary information on the potential toxicity of WO3 NPs and MPs.

Genotoxicity study of nickel oxide nanoparticles in female Wistar rats after acute oral exposure.

Nanoparticles (NPs) apart from their widespread advantages and increased utilisation, have aroused concerns over their safe use. Nickel (II) oxides (NiO) NPs are used as catalysts, biosensors and in many of the consumer products. The increasing use of NiO NPs necessitates an improved understanding of their potential impact on the environment and human health. In this study, we investigated the acute genotoxic effects of NiO NPs by oral route administration with three different doses (125, 250 and 500 mg/kg bw). Before the in vivo toxicological evaluation, characterisation of particles by Transmission Electron Microscopy, X-ray diffraction, Dynamic Light Scattering (DLS) and Laser Doppler Velocimetry analysis was performed. Genotoxicity biomarkers such as comet, micronucleus and chromosomal aberrations (CAs) assays were utilised in this study. To document the uptake, retention and elimination of the NPs, biodistribution studies were also performed. The particle size obtained from Transmission Electron Microscopy analysis for NiO NPs was 15.62 ± 2.59 nm. The mean hydrodynamic diameter and PdI of NiO NPs in Milli-Q water suspension obtained by DLS was 168.9 ± 17.13 nm and 0.375, respectively. Comet assay revealed significant (P < 0.001) DNA damage at 500 mg/kg bw dose in the PBL, liver and kidney cells of rats at the 24-h sampling time. The result of micronucleus and CAs tests was in agreement with the comet assay data. Biodistribution of NiO NPs revealed a maximum accumulation of Ni in the liver tissue at the 24-h sampling time. Our study showed significant DNA damage at the high dose level and the effect was more prominent at 24-h sampling time, providing preliminary evidence that the NiO NPs are capable of inducing genotoxicity when administered through the oral route. However, mechanistic investigations are needed before drawing any firm conclusion regarding the toxicology of NiO NPs.

Assessment of genotoxicity in female agricultural workers exposed to pesticides.

OBJECTIVE: This study was designed to determine the genotoxic effect of exposure to a mixture of pesticides in 106 female agricultural workers employed in cotton fields from India. METHODS: Comet, micronucleus and chromosomal aberrations tests were carried out in peripheral blood lymphocytes. Micronucleus test was also performed in buccal epithelial cells. Levels of antioxidant enzymes, RBC acetylcholinesterase and hematological parameters were analyzed in the blood samples of the study subjects. RESULTS: The results indicated significant DNA damage, increased frequency of micronuclei and chromosomal aberrations in the exposed subjects (p < 0.05). The levels of antioxidant enzymes were significantly lowered and the rate of lipid peroxidation was elevated in the exposed subjects. CONCLUSION: The outcome of the study revealed an increased risk of genotoxicity and health implications in female agricultural workers.