Browsing by Author "Sruthi, S"
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Item Assessing the systemic toxicity in rabbits after sub acute exposure of known ocular irritant chemicals(Toxicological Research, 2015-06) Reshma, SC; Sruthi, S; Syama, S; Gayathri, V; Mohanan, PVEye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenarioItem Biomedical application and hidden toxicity of zinc oxide nanoparticles(Materials Today Chemistry, 2019-01) Sruthi, S; Ashtami, J; Mohanan, PVZinc oxide nanoparticles (ZnO NPs) represent a novel type of metal oxide nanoparticles enabling a new horizon for biomedical applications spanning from diagnosis to treatment. ZnO NPs are extensively used in commercial products such as sunscreens and daily-care products. Apart from that, ZnO NPs are used in food packaging and ointments and as an antimicrobial and antifungal agent. They are extensively used for many biomedical applications noticeably in pharmaceutics and theranostics. Its exceptional optical, electrical, and physiochemical properties, notably its incredible surface chemistry, make ZnO NPs a reliable option for bioimaging, biosensors, antimicrobial action, and drug and gene delivery. The present review covers findings and developments in ZnO NPs research in relation to its application and toxicity mechanism. A special emphasis has been given to the neurotoxic potential of the ZnO NPs and glial cell toxicity. Various factors contributing to the toxic potential of ZnO NPs and cell signaling pathways concerning its toxicity are also discussed. Available data point toward the risk of uncontrollable use of zinc nanoformulation. With increasing use, ZnO NPs pose a severe threat both to the ecosystem and human beings. In a nutshell, the review outlines the current state of the art of ZnO NPs.Item Effect of dextran coated ferrite nanoparticles on the antioxidant defense mechanism of mice brain(Trends Biomat. Artif. Organs. 2014;20(4), 2015-02) Sruthi, S; Mohanan, PVToxicity of magnetic nanoparticles is mainly due to their ability to produce reactive oxygen species. Oxidative defense mechanism gets up regulated in response to ROS. The current study estimate the antioxidant level of mice brain in response to single time exposure of in-house synthesized dextran coated ferrite nanoparticles (DFN) administered via intraperitonial (IP) injection. Animals were randomly divided into 3 groups and were sacrificed in 7days interval. Antioxidant levels in the brain tissue homogenate were measured using standard protocols and compared with the antioxidant levels of control animals. No marked change in the antioxidant level was observed in any of the experimental group. All the values obtained were comparable to that of control. During the entire course of study, all the animals appeared healthy and showed no signs of behavioral problems. The study concludes that the in-house synthesized DFN intended for biomedical application do not cause any oxidative damage in the mice brain and is safe to use for further applications.Item Engineered Nanoparticles with Antimicrobial Property(Current Drug Metabolism, 2018-03) Reshma, VG; Syama, S; Sruthi, S; Reshma, SC; Remya, NS; Mohanan, PVAbstract: Background: The urge for the development and manufacture of new and effective antimicrobial agents is particularly demanding especially in the present scenario of emerging multiple drug resistant microorganisms. A promising initiative would be to converge nanotechnology to develop novel strategies for antimicrobial treatment. These distinct nano scale properties confer impressive antimicrobial capabilities to nanomaterials that could be exploited. Nanotechnology particularly modulates the physicochemical properties of organic and inorganic nanoparticles, rendering them suitable for various applications related to antimicrobial therapy compared to their bulk counterparts. However, a major issue associated with such usage of nanomaterials is the safety concern on heath care system. Hence, a thorough put knowledge on biocompatible nanostructures intended for antimicrobial therapy is needed. Methods: A systematic review of the existing scientific literature is being attempted here which includes the properties and applications of a few nano structured materials for antimicrobial therapy and also the mechanism of action of nanomaterials as antimicrobial agents. Silver (Ag), Graphene, Quantum dots (QDs), Zinc oxide (ZnO) and chitosan nanoparticles are taken as representatives of metals, semiconductors, metal oxides and organic nanoparticles that have found several applications in antimicrobial therapy are reviewed in detail. Results and Conclusion: An ideal anti microbial should selectively kill or inhibit the growth of microbes but cause little or no adverse effect to the host. Each of the engineered nanomaterials reviewed here has its own advantages and disadvantages. Nanomaterials in general directly disrupt the microbial cell membrane, interact with DNA and proteins or they could indirectly initiate the production of reactive oxygen species (ROS) that damage microbial cell components and viruses. Some like silver nanoparticles have broad spectrum antibacterial activity while others like cadmium containing QDs shows both antibacterial as well as antiprotozoal activity. Nano material formulations can be used directly or as surface coatings or as effective carriers for delivering antibiotics. Polycationic nature of Chitosan NPs helps in conjugation and stabilization of metallic nanoparticles which will enhance their effective usage in antimicrobial therapy.Item Engineered Zinc Oxide Nanoparticles; Biological Interactions at the Organ Level(Current Medicinal Chemistry, 2016-12) Sruthi, S; Mohanan, PVZinc oxide nanoparticles (ZnO NPs) are one of the widely used nanoparticles with spectrum of application, in the areas like daily care products, sensors, antibacterial agents, and biomedical sector. With extensive application the risk of exposure at occupational and consumer level also increases. Huge amount of data are available on the biointeraction of ZnO NPs. Though the toxicity of ZnO NPs is attributed to particle dissolution inside the cellular compartments and their ability to generate the reactive oxygen species, the ambiguity prevails over the exact mechanism of toxicity. The in vivo studies on different animal models and humans suggest different level of toxicity in these organisms. However the synthetic route, physiochemical properties of the nanoparticle, mode of exposure and nature of the test system often influences these studies. Hence the study results vary and sometimes contradict on one another. The current review focuses on the interaction of ZnO NPs with different organ systems. It also points to the factors to be considered while undertaking such studies in order to ensure reliability of the resultsItem Evaluation of Toxicity of Maura Reduced Graphene Oxide using In vitro Systems(J Nanomed Nanotechnol., 2014) Cherian, RS; Sreejith, R; Syama, S; Sruthi, S; Gayathri, V; Maekawa, T; Sakthikumar, D; Mohanan, PVThe intriguing properties of graphene has paved way for many potential biomedical applications like drug delivery, tissue engineered scaffold, bio sensing and so on. Here, we report the interaction of Maura reduced graphene oxide (MRGO) with the peripheral blood mononuclear cells (PBMNCs), as there is a likelihood of graphene coming in contact with the blood through intentional or accidental exposure. MRGO was synthesized by reducing graphene oxide using Halomonas Maura and autoclaved subsequently to prevent microbial contamination. It was characterized by TEM, AFM and FITR. Initial cytotoxicity was conducted in L929 cells to get the dose response. Oxidative stress potential, effect on proliferative capacity, genotoxicity and induction of apoptosis in PBMNCs treated with MRGO were assessed. MRGO elicited a dose dependent ROS generation which promoted apoptosis in PBMNCs. Proliferation of these cells were also found to be hindered. However, MRGO did not induce genotoxicity and generation of reactive nitrogen species. In conclusion MRGO shows a dose dependent toxicity in cells, generating ROS, inducing apoptosis and affecting proliferation, which may be due to the loss of exopolysaccharide coating due to autoclaving. This study raises a serious concern regarding the in vivo biomedical application of MRGO, where IV and IP are the main routes of exposure. Further evaluation is required regarding the interaction of autoclaved MRGO with the blood cells.Item In vitro interaction and biocompatibility of titanate nanotubes with microglial cells(Toxicology and Applied Pharmacology, 2018-08) Sruthi, S; Loiseau, A; Boudon, J; Sallem, F; Maurizi, L; Mohanan, PV; Lizardc, G; Millot, NTitanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis.Item Investigation on cellular interactions of astrocytes with zinc oxide nanoparticles using rat C6 cell lines(COLLOIDS AND SURFACES B-BIOINTERFACES, 2015) Sruthi, S; Mohanan, PVZinc oxide nanoparticles (ZnO NPs) are widely used in cosmetic industries and have also found important applications in electrical and chemical industries. It is well documented that inhaled ZnO NPs can reach the brain through the olfactory neuronal pathway and can interfere with the brain zinc homeostasis. Most of the studies focus on the toxicity of ZnO NPs on neuronal cells and microglia. Not much work is available on the bio interaction of ZnO NPs with astrocytes, the major cells involved in brain homeostasis. Therefore, this study focuses on the interaction of ZnO NPs with rat C6 glial cells. The results of this study reveal that the nanoparticles are taken up by the astrocytes and induce a time and dose dependent toxicological response which is indicated by the nanoparticle uptake studies and cell viability assays. Also the results of DCFH-DA (2',7'-dichlorofluorescein diacetate) assay show that the ZnO NPs induce strong oxidative stress in cells at 3 and 6 h. However, at 24 h the reactive oxygen species (ROS) detected in the nanoparticles treated groups were same as that of control. The mode of cell death induced by ZnO NPs was apoptosis as revealed by the nuclear condensation studies, live dead assay using acridine orange/ethidium bromide and apoptosis detection kit. This study, which explores the interaction of ZnO NPs with astrocytes, concludes that the persistence of particle can continue to have a damaging effect on the astrocytes. And hence the time of exposure and particle clearance by the system should be evaluated more thoroughly to prevent the health hazards due to these particles. (C) 2015 Elsevier B.V. All rights reserved.Item Investigation on cellular interactions of astrocytes with zinc oxidenanoparticles using rat C6 cell lines(Colloids and Surfaces B: Biointerfaces, 2015-07) Sruthi, S; Mohanan, PVZinc oxide nanoparticles (ZnO NPs) are widely used in cosmetic industries and have also found important applications in electrical and chemical industries. It is well documented that inhaled ZnO NPs can reach the brain through the olfactory neuronal pathway and can interfere with the brain zinc homeostasis. Most of the studies focus on the toxicity of ZnO NPs on neuronal cells and microglia. Not much work is available on the bio interaction of ZnO NPs with astrocytes, the major cells involved in brain homeostasis. Therefore, this study focuses on the interaction of ZnO NPs with rat C6 glial cells. The results of this study reveal that the nanoparticles are taken up by the astrocytes and induce a time and dose dependent toxicological response which is indicated by the nanoparticle uptake studies and cell viability assays. Also the results of DCFH-DA (2 ,7 -dichlorofluorescein diacetate) assay show that the ZnO NPs induce strong oxidative stress in cells at 3 and 6 h. However, at 24 h the reactive oxygen species (ROS) detected in the nanoparticles treated groups were same as that of control. The mode of cell death induced by ZnO NPs was apoptosis as revealed by the nuclear condensation studies, live dead assay using acridine orange/ethidium bromide and apoptosis detection kit. This study, which explores the interaction of ZnO NPs with astrocytes, concludes that the persistence of particle can continue to have a damaging effect on the astrocytes. And hence the time of exposure and particle clearance by the system should be evaluated more thoroughly to prevent the health hazards due to these particles.Item Zinc oxide nanoparticles mediated cytotoxicity, mitochondrial membrane potential and level of antioxidants in presence of melatonin(International Journal of Biological Macromolecules, 2017-06) Sruthi, S; Mohanan, PVZinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs. Melatonin is a hormone secreted by the pineal gland with great antioxidant properties. The melatonin is known to protect cells from ROS inducing external agents like lipopolysaccharides. In the present study,the protective effect of melatonin on ZnO NPs mediated toxicity was evaluated using C6 glial cells. The Cytotoxicity, mitochondrial membrane potential and free radical formation were measured to study the effect of melatonin. Antioxidant assays were done on mice brain slices, incubated with melatonin and ZnO NPs. The results of the study reveal that, instead of imparting a protective effect, the melatonin pre-treatment enhanced the toxicity of ZnO NPs. Melatonin increased antioxidant enzymes in brain slices.