Cadmium selenide (CdSe) quantum dots cause genotoxicity and oxidative stress in Allium cepa plants.

Quantum Dots (QDs), are considered as promising tools for biomedical applications. They have potential applications in agricultural industries, novel pesticide formulations, use in bio-labels and devices to aid genetic manipulation and post-harvest management. Since interactions with higher plants are of important environmental and ecological concern we investigated the cytotoxicity and genotoxicity of CdSe QDs in a model plant (Allium cepa) and established relationships between QDs genotoxic activity and oxidative stress. Allium cepa bulbs with intact roots were exposed to three concentrations of CdSe QDs (12.5, 25 and 50 nM). Cell viability and mitotic frequencies was measured for cytotoxicity, and to assess the genotoxicity DNA lesions, chromosome aberrations and micronuclei were evaluated. We report that QDs exerted significant genotoxic effects, associated with oxidative stress. This could be correlated with the retention of Cd in Allium roots as a dose-dependent increase with the highest uptake at 50 nM of CdSe QD. Oxidative stress induced by CdSe QD treatment activated both, antioxidant (SOD, CAT) scavengers and antioxidant (GPOD, GSH) enzymes. Concentrations as low as 25 nM CdSe QDs were cytotoxic and 50 nM CdSe QDs was found to be genotoxic to the plant. These findings enable to determine the concentrations to be used when practical applications using nanodevices of this type on plants are being considered.

Investigating the underlying mechanism of cadmium-induced plant adaptive response to genotoxic stress.

Plants as sessile organisms have developed some unique strategies to withstand environmental stress and adaptive response (AR) is one of them. In the present study Cadmium (Cd)-induced AR was evaluated to ameliorate the genotoxicity of a known chemical mutagen ethyl methanesulphonate (EMS) based on cytotoxicity, genotoxicity and oxidative stress in two model plant systems Allium cepa L. and Vicia faba L. Priming the plants with cadmium chloride (CdCl2, 25 and 50 µM) reduced the genotoxicity of EMS (0.25 mM). Cd-induced AR was evident by the magnitude of adaptive response (MAR) values calculated for cytotoxicity, genotoxicity and biochemical parameters. In addition the involvement of some major metabolic pathways and epigenetic modifications in AR was investigated. Metabolic blockers of protein kinase cascades, DNA repair, oxidative stress and de novo translation interfered with the adaptive response implying their role in AR whereas, inhibitors involved in post-replication repair and autophagy were ineffective implicating that they probably have no role in the AR studied. Moreover to find the role of DNA methylation in AR, methylation-sensitive comet assay was carried out. Simultaneously 5-methyl- 2'-deoxycytidine (5mdC) levels were quantified by HPLC (high performance liquid chromatography). AR was eliminated in cells treated with a demethylating agent, 5-aza- 2'deoxycytidine (AZA). Results implied a contribution of DNA hypermethylation. To the best of our knowledge this is a first report correlating DNA methylation to Cd-induced adaptive response in plants undergoing genotoxic stress.

Effect of low-dose exposure of aluminium oxide nanoparticles in Swiss albino mice: Histopathological changes and oxidative damage.

Rapid growth in the use of aluminium oxide nanoparticles (Al2O3 NPs) in various fields such as medicine, pharmacy, cosmetic industries, and engineering creates concerns since the literature is replete with data regarding their toxicity in living organisms. The objective of the present study was to demonstrate the potential toxicological manifestations of repeated exposure to Al2O3 NP at low doses in vivo. In the present study, Al2O3 NP was orally administered at 15, 30 or 60 mg kg-1 body weight for 5 days to Swiss albino male mice. A battery of well-defined assays was undertaken to evaluate aluminium (Al) bioaccumulation, haematological and histological changes, oxidative damage and genotoxicity. Physico-chemical characterisation demonstrated increases in hydrodynamic diameter along the concentration gradient of Al2O3 NP dispersed in MilliQ water. Brain, liver, spleen, kidney and testes showed high Al retention levels. Histopathological lesions were prominent in the brain and liver. Al2O3 NP treatment increased levels of lipid peroxidation and decreased glutathione content in the test organs at all dose levels. The enzyme activities of catalase and superoxide dismutase were also significantly altered. DNA damage quantified using the comet assay was markedly increased in all the soft organs studied. Anatomical abnormalities, redox imbalance and DNA damage were positively correlated with Al retention in the respective organs. Size, zeta potential and colloidal state might have contributed to the bio-physico-chemical interactions of the NPs in vivo and were responsible for the non-linear dose response. The overall data indicate that Al2O3 NP exposure may result in adverse health consequences, inclusive of but not limited to disturbed redox homeostasis, hepatocellular toxicity, neurodegeneration and DNA damage.

Genotoxicity and biocompatibility of superparamagnetic iron oxide nanoparticles: Influence of surface modification on biodistribution, retention, DNA damage and oxidative stress.

Superparamagnetic iron oxide nanoparticles (SPION) require stable surface modifications to render safe nanocapsules for biomedical applications. Herein, two types of surface modified poly(lactic-co-glycolic acid)-encapsulated SPION were synthesized using either α-tocopheryl-polyetheleneglycol-succinate (TPGS) or didodecyl-dimethyl-ammonium-bromide (DMAB) as surfactants by emulsification. SPION-TPGS (180 nm) was larger than SPION-DMAB (25 nm) and uncoated SPION (10 nm). Both formulations were positively charged and induced lower cyto-genotoxicity and ROS generation than uncoated SPION in human lymphocytes. SPION-DMAB was least cyto-genotoxic among the three. Based on these results, mice were gavaged with the formulations for 5 consecutive days and biocompatibility studies were performed on the 7th and 21st days. ICP-AES and Prussian blue staining revealed the internalization of SPION-DMAB in brain and spleen, and SPION-TPGS in liver and kidney on day 7. This was correlated with high DNA damage and oxidative stress in the same organs. Substantial clearance of Fe was accompanied by reduced genotoxicity and oxidative stress on day 21. Therefore, SPION-DMAB can be further studied for oral drug delivery to the brain and imaging of cerebral tissue without any functional ligand or external magnetic field.

Oxidative stress responses of two different ecophysiological species of earthworms (Eutyphoeus waltoni and Eisenia fetida) exposed to Cd-contaminated soil.

The aim of this study was to assess the biomarkers of oxidative stress [reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), aldehyde dehydrogenase (ALDH) and lipid peroxidation (LPO)] in earthworms of different ecological categories [epigeic Eisenia fetida (E. fetida) and anecic Eutyphoeus waltoni (E. waltoni)] exposed to cadmium (Cd)-polluted soil (30, 60 and 120 mg kg-1) for 28 days. Cd accumulation in earthworms increased significantly with increasing exposure dose and duration. However, E. fetida showed a relatively higher level of Cd accumulation until day 21; thereafter, depletion in the Cd level was recorded for the highest exposure dose. In E. waltoni, the detoxification enzymes and GSH level increased significantly with increasing exposure dose and Cd accumulation for 14 days (acute phase). In contrast, in E. fetida, acute exposure to Cd increased detoxification enzymes with decrease in GSH levels. For both species, sub-chronic exposures (28 days) increased lipid peroxidation with decrease in detoxification enzymes. GPx and ALDH responses of Cd-exposed earthworms showed a similar trend. Thus, these enzymes can be used as general biomarkers in these two species. The consistent variations in GST, GPx and ALDH activities suggest that E. waltoni may be used as a bioindicator species; this further signifies the use of endemic earthworms as a bioindicator to assess the risk of soil contamination. The present investigation indicates that Cd accumulation and biomarker responses in earthworms depend on dose and duration of exposure and on the concerned species.

Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.

CONTEXT: Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. OBJECTIVE: In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. MATERIALS AND METHODS: Human lymphocytes were exposed to orlistat (250, 500 and 1000 µg/ml), sibutramine (250, 500 and 1000 µg/ml) and caffeine (25, 50, 75, 100, 125 and 150 µg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 µg/ml) and a single concentration of orlistat (250 µg/ml). RESULTS: Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 µg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 µg/ml) of caffeine lead to a decrease in DNA damage. DISCUSSION AND CONCLUSION: Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.