Biocompatibility assessment of bovine serum albumin conjugated manganese dioxide nanoparticle and their therapeutic role against microwave radiation induced haematological toxicity in male Wistar rats.

Microwave (MW) radiations are widely used in communications, radar and medical treatment and thus human exposure to MW radiations have increased tremendously, raising health concerns as MW has been implicated in induction of oxidative stress condition in our body. Few metallic nanoparticles (NPs) have been shown to mimic the activity of antioxidant enzymes and hence can be applied for the modulation of adverse effects caused by MW. Present study aimed to assess the biocompatibility of Bovine serum albumin (BSA) conjugated manganese dioxide nanoparticles (MNP*) and to counteract the impact of MW on the haematological system of male Wistar rats. Experiments were conducted in two sets. Set I involved biodistribution and antioxidant activity evaluation of MNP* at different doses. Results showed a dose-dependent increase in antioxidant potential and significant biodistribution in the liver, spleen, kidney, and testis, with no organ damage, indicating its biocompatibility. Experiment set II constituted the study of separate and combined effects of MW and MNP* on haematological parameters, oxidative status, and genotoxic study in the blood of rats. MW exposure significantly altered red blood cell count, hemoglobin, packed cell volume percentage, monocyte percentage, aspartate aminotransferase, Alanine aminotransferase and uric acid. MW also induced significant DNA damage in the blood. A significant increase in lipid peroxidation and a decrease in antioxidant enzyme superoxide dismutase was also observed in MW exposed group. However, these alterations were reduced significantly when MNP* was administered. Thus, MNP* showed biocompatibility and modulatory effects against MW-induced alterations in the haematological system of rats.

Bioaccumulation of CdSe Quantum Dots Show Biochemical and Oxidative Damage in Wistar Rats.

Cadmium selenium quantum dots (CdSe QDs) with modified surfaces exhibit superior dispersion stability and high fluorescence yield, making them desirable biological probes. The knowledge of cellular and biochemical toxicity has been lacking, and there is little information on the correlation between in vitro and in vivo data. The current study was carried out to assess the toxicity of CdSe QDs after intravenous injection in Wistar male rats (230 g). The rats were given a single dose of QDs of 10, 20, 40, and 80 mg/kg and were kept for 30 days. Following that, various biochemical assays, hematological parameters, and bioaccumulation studies were carried out. Functional as well as clinically significant changes were observed. There was a significant increase in WBC while the RBC decreased. This suggested that CdSe quantum dots had inflammatory effects on the treated rats. The various biochemical assays clearly showed that high dose induced hepatic injury. At a dose of 80 mg/kg, bioaccumulation studies revealed that the spleen (120 g/g), liver (78 g/g), and lungs (38 g/g) accumulated the most. In treated Wistar rats, the bioretention profile of QDs was in the following order: the spleen, liver, kidney, lungs, heart, brain, and testis. The accumulation of these QDs induced the generation of intracellular reactive oxygen species, resulting in an alteration in antioxidant activity. It is concluded that these QDs caused oxidative stress, which harmed cellular functions and, under certain conditions, caused partial brain, kidney, spleen, and liver dysfunction. This is one of the most comprehensive in vivo studies on the nanotoxicity of CdSe quantum dots.

A Perspective on Reproductive Toxicity of Metallic Nanomaterials.

Nanotechnological tools have been greatly exploited in all possible fields. However, advancement of nanotechnology has raised concern about their adverse effects on human and environment. These deleterious effects cannot be ignored and need to be explored due to safety purpose. Several recent studies have demonstrated possible health hazard of nanoparticles on organism. Moreover, studies showed that toxicity of metallic nanomaterial could also lead to reproductive toxicity. Various deleterious effects have demonstrated decreased sperm motility, increased abnormal spermatozoa, altered sperm count, and altered sperm morphology. Morphological and ultrastructural changes also have been reported due to the accumulation of these nanomaterials in reproductive organs. Nonetheless, studies also suggest crossing of metallic nanoparticles through blood testes barrier and generation of oxidative stress which plays major role in reproductive toxicity. In the present study, we have incorporated updated information by gathering all available literature about various metallic nanomaterials and risk related to reproductive system.

Cumulative effects of manganese nanoparticle and radiofrequency radiation in male Wistar rats.

Radiofrequency radiation (RFR) is a type of non-ionizing electromagnetic radiation that includes radiowaves and microwaves with a frequency range between 3 KHz and 300 GHz. Mobile phones operate with RFR and are used tremendously resulting in increased and continuous exposure of humans to these radiations. On the other hand, nanoparticles are also being used extensively in various fields. The increasing use of radiofrequency radiations and nanoparticles has become a concern to the general public. Not many studies have reported the cumulative effect of these stressors. Hence, the present investigation was aimed to find out their cumulative effect on the mammalian system. In this study manganese nanoparticles (MNPs) were synthesized and characterized. Adult male Wistar rats were exposed to MNPs and mobile phone radiation for 45 days and their separate, as well as cumulative impact, was investigated. The effect of the MNPs and RFR on liver, kidney, and reproductive parameters were studied. Histopathology as well as liver and kidney parameters were altered when exposed to MNPs and RFR separately. However, their combined treatment did not show a synergistic toxic response in liver and kidney functions which may be due to the fact that the radiation level is low, specific absorption rate (SAR) is subthermal (0.04 W/kg) and liver and kidney are located intra abdominally, hence they would absorb comparatively lesser radiation than the testicles. MNPs and RFR both caused a highly significant decrease in sperm count, which further decreased in the combined treatment (MNPs + RFR). These results indicate that the combined treatment of these stressors can have an additive toxic response to the male reproductive system.

Metal accumulation and health risk assessment in wastewater used for irrigation around the Agra Canal in Faridabad, India.

Wastewater application for irrigation is a traditional and economic tool in developing nations. Yet prolonged use of wastewater for agricultural activities contributes to the accumulation of metals in both soil and vegetables. This study investigated the accumulation and contamination of vegetables with heavy metals ensuing from the application of wastewater from the Agra Canal and the associated risks posed to human health. Three sites across the Agra canal were selected for sampling (CW-1, CW-2, and CW-3), where untreated wastewater is being used to irrigate vegetables (spinach, coriander, radish, and garlic crops), for which tube-well water (TW) from a village served as the control site. Water, soil, and vegetable samples were collected from all sites. The presence in them of various metals, such as As, Pb, Cr, Mn, Cu, Zn, and Ni, was detected at all four sites. The greatest content of Mn was found in CW-1's water (7.91 mg/L), soil (633.77 mg/kg), and in spinach 368.12 (mg/kg) grown there. Significantly higher metal concentrations were observed in vegetables irrigated with wastewater than in tube-well-irrigated vegetables, with the metals ranked in accumulation as follows Mn > Zn > Ni > Cu > Cr > Pb > As. Our results also revealed that metal bioaccumulation varied enormously between foliar and non-foliar vegetables, as well as among the four sites. Daily metal intake (DMI) and health risk index (HRI) analyses suggested that children consuming contaminated vegetables are at higher risk than adults. The HRI for Mn, Ni, and Pb was above 1, which indicated significant health hazards to humans consuming the wastewater-irrigated vegetables. Moreover, the control site where tube-well water was used had an HRI below 1, signifying a negligible health risk for its consumption. Therefore, we may conclude that the extensive application of contaminated water for a longer duration would likely further increase metal accumulation in soil and vegetables that may be hazardous to living organisms.

Iron oxide nanoparticle-induced hematopoietic and immunological response in rats.

The application and use of iron oxide nanoparticless (IONPs) in the biomedical field are steadily increasing, although it remains uncertain whether IONPs are safe or should be used with caution. In the present study, we investigated the toxicity profile of ultrafine IONPs in rats administered with 7.5, 15 and 30 mg IONPs/kg body wt intravenously once a week for 4 weeks. IONP treatment reduces bone marrow-mononuclear cell proliferation, increases free radical species and DNA damage leading to growth arrest and subsequently apoptosis induction at 15 and 30 mg doses. It also induces apoptosis in undifferentiated hematopoietic stem cells. IONP treatment significantly increased the pro-inflammatory cytokine (Interleukin (IL)-1ß, TNF-α, and IL-6) level in serum. The induction in inflammation was likely mediated by splenic M1 macrophages (IL-6 and TNF-α secretion). IONP treatment induces splenocyte apoptosis and alteration in the immune system represented by reduced CD4+/CD8+ ratio and increased B cells. It also reduces innate defense represented by lower natural killer cell cytotoxicity. IONP administration markedly increased lipid peroxidation in the spleen, while the glutathione level was reduced. Similarly, superoxide dismutase activity was increased and catalase activity was reduced in the spleen of IONP-treated rats. At an organ level, IONP treatment did not cause any significant injury or structural alteration in the spleen. Collectively, our results suggest that a high dose of ultrafine IONPs may cause oxidative stress, cell death, and inflammation in a biological system.

Biodistribution, Clearance And Morphological Alterations Of Intravenously Administered Iron Oxide Nanoparticles In Male Wistar Rats.

INTRODUCTION: Nanoparticles are used worldwide because of their unique properties, with large-scale application in various fields, such as medicine, cosmetics and industries. In view of their widespread use, the potential adverse effects of nanoparticles have become a significant cause for concern, in terms of not only human health and safety but also the environment. The present investigation focused on establishing the bioaccumulation patterns and ultrastructural changes induced by retained iron oxide nanoparticles (IONPs) in various target organs of rats. METHODS: Twenty-four male Wistar rats were randomly divided into four groups. Experimental animals were intravenously administered different doses of IONPs (7.5 mg/kg, 15 mg/kg and 30 mg/kg) once in a week for 4 weeks. Urine and feces samples were collected on a daily basis to assess nanoparticle clearance and analyzed via atomic absorption spectroscopy (AAS). At the end of the experiment, rats were euthanized and different organs, including spleen, liver, kidney, lung, heart, testis and brain, were dissected. Bioaccumulation of iron in organs and ultrastructural changes induced by IONPs were determined. RESULTS: The maximal concentration of iron was detected in spleen and minimal concentration in the brain. The level of iron accumulation in organs was as follows: spleen>blood>liver>kidney>lung>heart>testis>brain. The excretion profile in urine revealed maximum excretion on the day following administration that was maintained until day 28, whereas the iron content in feces remained high during the first three days after injection. A similar pattern was observed throughout the duration of the experiment. Ultrastructural alterations were detected in spleen, kidney, lung, heart, testis, brain and liver, indicative of cellular damage induced by accumulating nanoparticles in these organs. CONCLUSION: Intravenous administration of IONPs results in ultrastructural changes and dose-dependent bioaccumulation in different organs of rats.

PLGA-CTAB curcumin nanoparticles: Fabrication, characterization and molecular basis of anticancer activity in triple negative breast cancer cell lines (MDA-MB-231 cells).

Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells). In in-vitro drug release assay, Cur was released from CN by flicking diffusion and anomalous transport process. CN showed a higher cellular incorporation than free Cur resulted in higher cytotoxicity. Checking the anticancer activity at the molecular level, Cur has shown to induce the reactive oxygen species production that subsequently causes the DNA damage and resulting in p38-MAPK activation. The p38-MAPK induce the expression of p16/INKK4a, p21/waf1/cip1 and p53 resulting in a reduction in the level of CDK2, CDK4, cyclin D1 and cyclin E and subsequently cell cycle arrest at G1/S and G2/M phase. It also reduces the expression of DNA repair gene, i.e. BRCA1, BRCA2, Rad51, Rad50, Mre11 and NBS1 resulting in apoptosis induction due to persistent DNA damage. This study presents an effective delivery of curcumin in TNBC cancer cells and it could open the new frontiers in clinical cancer chemotherapy.

Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes.

Over the past few decades nanotechnology and material science has progressed extremely rapidly. Iron oxide nanoparticles (IONPs) owing to their unique magnetic properties have a great potential for their biomedical and bioengineering applications. However, there is an inevitable need to address the issue of safety and health effects of these nanoparticles. Hence, the present study was aimed to assess the cytotoxic effects of IONPs on rats' lymphocytes. Using different assays, we studied diverse parameters including mitochondrial membrane potential, intracellular accumulation of reactive oxygen species (ROS), lactate dehydrogenase activity, antioxidant enzymes activity and DNA damage measurements. Intracellular metal uptake and ultrastructure analysis were also carried out through inductively coupled plasma atomic emission spectroscopy, transmission electron microscopy respectively. The results show that the IONP-induced oxidative stress was concentration-dependent in nature, with significant (P < 0.05) increase in ROS levels, lipid peroxidation level as well as depletion of antioxidant enzymes and glutathione. Moreover, we observed morphological changes in the cell after intracellular uptake and localization of nanoparticles in cells. From the findings of the study, it may be concluded that IONPs induce ROS-mediated cytotoxicity in lymphocytes. Copyright © 2017 John Wiley & Sons, Ltd.