Browsing by Author "Sreekanth, PJ"

Now showing 1 - 6 of 6
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    Cells-nano interactions and molecular toxicity after delayed hypersensitivity, in Guinea pigs on exposure to hydroxyapatite nanoparticles
    (COLLOIDS AND SURFACES B-BIOINTERFACES, 2013) Geetha, CS; Remya, NS; Leji, KB; Syama, S; Reshma, SC; Sreekanth, PJ; Varma, HK; Mohanan, PV
    The aim of the study was to evaluate the cells-nanoparticle interactions and molecular toxicity after delayed hypersensitivity in Guinea pigs, exposed to hydroxyapatite nanoparticles (HANP). The study focuses on synthesizing and characterizing HANPs and gaining an insight into the cytotoxicity, molecular toxicity, hypersensitivity and oxidative stress caused by them in vitro and in vivo. HANP was synthesized by chemical method and characterized by standard methods. Cytotoxicity was assessed on L929 cells by MTT assay and in vitro studies were carried out on rat liver homogenate. In vivo study was carried out by topical exposure of Guinea pigs with HANP, repeatedly, and evaluating the skin sensitization potential, blood parameters, oxidative stress in liver and brain and DNA damage (8-hydroxyl-2-deoxyguanosine: 8-OHdG) in liver. The results of the study indicated that there was no cytotoxicity (up to 600 mu g/mL) and oxidative damage (up to 100 mu g/mL), when exposed to HANPs. It was also evident that, there was no skin sensitization and oxidative damage when HANP were exposed to Guinea pigs. (C) 2013 Elsevier B.V. All rights reserved.
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    Determination of antioxidant defense mechanism after acute oral administration of hydroxyapatite nanoparticles in rats.
    (J Free Rad Antioxidants, 2014-03) Reshma, SC; Syama, S; Leji, B; Anju, M; Sreekanth, PJ; Varma, HK; Mohanan, PV
    Hydroxyapatite nanoparticle (HANPs) has various applications like bone grafting, dental fillings, in toothpastes and mouth washes for teeth remineralization, etc. Even though HANPs application is a widely investigated area of research, the toxicity aspect still remains largely unexplored. This study focuses on the acute oral toxicity of HANPs exposed to Wistar rats, as its prospective application involve exposure via the oral route. In-house synthesized HANPs (<50 nm) was administered to rats orally. Hematological and biochemical parameters were carried out in blood from these animals. After sacrifice, gross necropsy was conducted and lipid peroxidation (LPO) and antioxidant status was estimated in the liver. During the experimental period, no HANPs related toxicity was observed and the hematological and biochemical parameters remained similar to control. However, dose dependent LPO in liver but the resultant oxidative stress was combated by the cells innate antioxidant defense mechanisms, which was evident with the increase in activity. Even though no death or adverse toxic effects were observed in the acute oral toxicity (unclassified compound as per Globally Harmonized System for Classification for chemical substances and mixtures) according to OECD 423, there was a dose dependant increase in the oxidative stress.
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    Effect of Zinc Oxide nanoparticles on cellular oxidative stress and antioxidant defense mechanisms in mouse liver
    (TOXICOLOGICAL AND ENVIRONMENTAL CHEMISTRY, 2013) Syama, S; Reshma, SC; Sreekanth, PJ; Varma, HK; Mohanan, PV
    Zinc oxide nanoparticles (ZnO2), a common ingredient of cosmetics has a huge variety of applications. Previous studies reported oxidative stress mediated toxicity of ZnO2 nanoparticles on various mammalian cell lines. Although zinc (Zn) is an essential mineral at higher concentrations this metal is toxic. The present study focused on size determination by monitoring changes in activities of antioxidant defense mechanism in response to oxidative stress induced by ZnO2 nanoparticles using mouse liver tissue homogenates. The study also investigated effects of oxidative stress induced DNA damage by determining formation of 8-OHdG in mouse liver homogenate. A cytotoxicity assay was also carried out in L929 cells to determine cell viability. The results of the study indicated that 50g/ml of ZnO2 nanoparticles induced 50% cell death. Alterations in antioxidant parameters and 8-OHdG were also noted. Data showed that there was a concentration-dependent fall in cell viability, decrease antioxidant enzyme levels and increase formation of DNA adduct (8-OHdG) when mouse liver tissue homogenate were exposed to ZnO2 nanoparticles.
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    Molecular toxicity of dextran coated ferrite nanoparticles after dermal exposure to Wistar rats
    (J of Toxicology and Health, 2014-03) Mohanan, PV; Syama, S; Sabareeswaran, A; Sreekanth, PJ; Varma, HK
    Dextran coated ferrite nanomaterials (DFNM) of size <25 nm was synthesized, characterized and analyzed for systemic toxicity at the molecular level by in vitro and in vivo methods. Skin, the external barrier is one of the main portals of nanoparticles entry upon accidental exposure in work place. In the present study, DFNM was dermally applied on the skin of Wistar rats to monitor the translocation of nanomaterials from the route of entry and subsequent systemic toxicity. At the end of 28 days of exposure, blood was collected and subjected to haematological and biochemical analysis. Gross necropsy was conducted and major organs were collected for histopathological observations. Liver samples of both the in vitro and in vivo studies were evaluated for the production of LPO, activity of GR, GPx, SOD, total GSH and level of 8-OHdG formed. The results demonstrated that there were no significant fluctuations in the level of antioxidant systems, lipid peroxidation, haematological, biochemical, or histopathological lesions. Least amount of increase in 8-OHdG was observed in the in vitro samples. Hence, it can be concluded that the synthesized DFNM was non-toxic on dermal exposure and fails to induce any potential damages in the vital organs functions.
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    Toxicity evaluation of dextran coated ferrite nanomaterials after acute oral exposure to Wistar rats.
    (J Allergy Ther, 2014) Syama, S; Reshma, SC; Leji, B; Anju, M; Sreekanth, PJ; Varma, HK; Mohanan, PV
    Dextran Coated Ferrite Nanomaterials (DFNM) of size <25 nm was synthesized, characterized and the acute oral toxicity along with antioxidant enzymes activities were evaluated in Wistar rats. The healthy adult rats were orally administered with 300 and 2000 mg/kg body weight of DFNM using a gastric needle and observed for 14 days. None of the animals showed any adverse effects/toxicity at the end of observation period. After two weeks of administration, blood was collected and subjected to haematological and biochemical analysis. Animals were sacrificed and gross necropsy was done on all animals. Liver was dissected; homogenized (10% homogenate) and rate of formation of lipid peroxides were evaluated. In addition, the concentration of reduced glutathione and the activity of vital antioxidant enzymes like glutathione reductase, glutathione peroxidase and superoxide dismutase was determined. The result of the study indicates that even at 2000 mg/kg body weight, DFNM was non-toxic. It was also observed that there was a slight fluctuation in the level of antioxidant enzymes activity, lipid peroxidation, haematological and biochemical parameters but it was not significant. Hence, it can be concluded that the in-house synthesized DFNM was non-toxic and shows no lethal effects when orally exposed to rats.
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    Zinc Oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells
    (Toxicol Mech Methods, 2014-12) Syama, S; Sreekanth, PJ; Varma, HK; Mohanan, PV
    Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO2 and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6–8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn+ ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.