Browsing by Author "Reshma, SC"
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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 Assessment of hydroxyapatite nanoparticles induced oxidative stress- An in vitro study.(J Free Rad Antioxidants, 2014) Syama, S; Reshma, SC; Gayathri, V; Varma, HK; Mohanan, PVItem 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, PVThe 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.Item 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, PVHydroxyapatite 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.Item 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, PVZinc 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.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 Evaluating systemic toxicity in Rabbits after acute ocular exposure to irritant chemicals.(Advances in Toxicology., 2014) Reshma, SC; Mohanan, PVAcute systemic toxicity via ocular exposure route is not a well understood aspect.Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide) for 24 h and scored. After a period of 72 h, blood was collected from the animals for examining the hematological and biochemical parameters.The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario.Item Nano-biointeractions of PEGylated and bare reduced graphene oxide on lung alveolar epithelial cells: A comparative in vitro study(Colloids and Surfaces B: Biointerfaces, 2016-01) Reshma, SC; Syama, S; Mohanan, PVGraphene and its derivatives have garnered significant scientific interest and have potential use in nano-electronics as well as biomedicine. However the undesirable biological consequence, especially upon inhalation of the particle, requires further investigations. This study aimed to elucidate the nanobiointeractions of PEGylated reduced graphene oxide (PrGO) and reduced graphene oxide (rGO) with that of lung alveolar epithelial cells (A549). Both nanomaterials showed dose dependent decrease in cell viability and alteration of cell morphology after 24 h. Upon intracellular uptake of PrGO, it elicited oxidative stress mediated apoptosis in the cells by inducing ROS, loss of mitochondrial membrane potential (MMP) and inflammatory response by NF-B activation. Conversely, rGO was found to scavenge ROS efficiently except at high dose after 24 h. It was found that ROS at high dose of rGO prompted loss of MMP. rGO was found to adhere to the cell membrane, where itis assumed to bind to cell surface Toll like receptors (TLRs) thereby activating NF-B mediated inflammatory response. All these events culminated in an increase in apoptosis of A549 cells after 24 h of rGO exposure. It was also noticed that both the nanomaterials did not initiate lysosomal pathway but instead activated mitochondria mediated apoptosis. This study highlights the possible adverse toxic effect of PrGO and rGO upon inhalation and persistence of these particles in the lungs. Further research is required to comprehend the biological response of PrGO and rGO so as to advance its biomedical application and safety.Item 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, PVDextran 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.