Browsing by Author "Syama, S"
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Item An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behaviour(COLLOIDS AND SURFACES B-BIOINTERFACES, 2014) Remya, NS; Syama, S; Gayathri, V; Varma, HK; Mohanan, PVMesenchymal stem cells or multipotent progenitor cells isolated from bone marrow presents close resemblance to the natural in vivo milieu and hence preferred more than the conventional cell culture systems to predict the toxicological behavior of bio-nano interaction. The objective of the present study is to evaluate the molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal arrangement, oxidative stress response and apoptotic behavior with the confluent BMSCs as per standard protocols. The results of the MIT assay indicated that HANPs does not induce cytotoxicity up to 800 mu g/mL. It was also observed that oxidative stress related apoptosis and reactive oxygen species (ROS) production following nanoparticle treatment was similar to that of control (cells without treatment). Hence it can be concluded that the in-house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for evaluating the preliminary toxicity of nanomaterials. (C) 2014 Elsevier B.V. All rights reserved.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 Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice(Molecular Biology International, 2015-10) Syama, S; Gayathri, V; Mohanan, PVIn this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF 𝛽) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF 𝛽. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice.Item Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice(Molecular Biology International., 2015-12) Syama, S; Gayathri, V; Mohanan, PVIn this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF β) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF β. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice.Item 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 Comprehensive Application of Graphene: Emphasis on Biomedical Concerns(Nano Micro Letters., 2019-01) Syama, S; Mohanan, PVGraphene, sp2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional (2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a scaffold for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications. Open image in new windowItem 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 Determination of oxidative stress related toxicity on repeated dermal exposure of hydroxyapatite nanoparticles in rats(Intl. J. Biomaterials. 2014, 2015-02) Mohanan, PV; Syama, S; Sabareeswaran, AItem Development of a 3D multifunctional collagen scaffold impregnated with peptide LL-37 for vascularised bone tissue regeneration(Int J Pharm., 2024-01) Megha, KB; Syama, S; Sangeetha, VP; Vandana, U; Oyane, A; Mohanan, PVBone is a highly dynamic connective tissue that provides structural support, locomotion and acts as a shield for many vital organs from damage. Bone inherits the ability to heal after non-severe injury. In case of severe bone abnormalities due to trauma, infections, genetic disorders and tumors, there is a demand for a scaffold that can enhance bone formation and regenerate the lost bone tissue. In this study, a 3D collagen scaffold (CS) was functionalized and assessed under in vitro and in vivo conditions. For this, a collagen scaffold coated with hydroxyapatite (Ap-CS) was developed and loaded with a peptide LL-37. The physico-chemical characterisation confirmed the hydroxyapatite coating on the outer and inner surfaces of Ap-CS. In vitro studies confirmed that LL-37 loaded Ap-CS promotes osteogenic differentiation of human osteosarcoma cells without showing significant cytotoxicity. The efficacy of the LL-37 loaded Ap-CS for bone regeneration was evaluated at 4 and 12 weeks post-implantation by histopathological and micro-CT analysis in rabbit femur defect model. The implanted LL-37 loaded Ap-CS facilitated the new bone formation at 4 weeks compared with Ap-CS without LL-37. The LL-37 loaded Ap-CS incorporating apatite and peptide LL-37 would be useful as a multifunctional scaffold for bone tissue engineering.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 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 An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behavior(Colloids Surf B Biointerfaces, 2014-05) Remya, NS; Syama, S; Gayathri, V; Varma, HK; Mohanan, PVMesenchymal stem cells or multipotent progenitor cells isolated from bone marrow presents close resemblance to the natural in vivo milieu and hence preferred more than the conventional cell culture systems to predict the toxicological behavior of bio-nano interaction. The objective of the present study is to evaluate the molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal arrangement, oxidative stress response and apoptotic behavior with the confluent BMSCs as per standard protocols. The results of the MTT assay indicated that HANPs does not induce cytotoxicity up to 800 μg/mL. It was also observed that oxidative stress related apoptosis and reactive oxygen species (ROS) production following nanoparticle treatment was similar to that of control (cells without treatment). Hence it can be concluded that the in-house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for evaluating the preliminary toxicity of nanomaterials.Item Interfacing of dextran coated ferrite nanomaterials with cellular system and delayed hypersensitivity on Guinea pigs(COLLOIDS AND SURFACES B-BIOINTERFACES, 2014) Mohanan, PV; Geetha, CS; Syama, S; Varma, HKThe study focused on the interfacing of dextran coated ferrite nanomaterials (DFNM) with the cellular system and delayed hypersensitivity on Guinea pigs. In vitro study investigated the cytotoxic potential of DFNM on L929 cells, effect on antioxidant enzymes and Lipid peroxides (LPO) production on rat brain homogenates. DFNM was also repeatedly exposed topically to Guinea pigs for the evidence of skin sensitization and toxicity at the molecular level. Biochemical and hematological parameters were estimated. Liver and brain of Guinea pigs were homogenized and evaluated for the induction of LPO, glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and 8-hydroxyl-2-deoxyguanosine (8-OHdG). The results of the study demonstrated that there was no significant alternation in the level of antioxidant defense enzymes, LPO, hematological, biochemical or oxidative stress related DNA damage. Hence, it can be concluded that the synthesized DFNM was non-skin irritant or non-toxic at the molecular level under the laboratory conditions. (C) 2013 Elsevier B.V. All rights reserved.Item Investigation of chronic toxicity of hydroxyapatite nanoparticles administered orally for one year in wistar rats(Materials Science and Engineering, 2017-04) Remya, NS; Syama, S; Sabareeswaran, A; Mohanan, PVAlthough the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12 months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study.Item Microfluidic based human-on-a-chip: A revolutionary technology in scientific research(Trends in Food Science & Technology, 2021-04) Syama, S; Mohanan, PVBackground Detrimental drug toxicity and failure in efficacy during clinical trials is one of the major hurdles faced by the pharmaceutical companies. Conventionally, preclinical safety evaluation is performed in 2D cell cultures and animal models. However, the response of a drug seen in laboratory animals and cells grown as monolayers differs from how cells inside a human body respond. This is due to the lack of multi-organ interaction in cell cultures and species specificity between animal and human. Scope and approach Recently, progress in organ-on-a-chip (OoC) including multi-organ-on-a-chip (MoC) platform offers fast and cost-effective alternative approach to screen drugs authentically. Advanced human-on-a-chip (HoC) consists of several human organs held together in a hierarchical and physiological pattern crafting an in vitro human model. HoC recapitulates the structural and functional integrity of human system and overcomes the limitations of traditional protocols and inaccessibility to human models. Key findings In HoC, cells are cultured in a sterile controlled environment that allows manipulation of physico-chemical factors, monitoring molecular and functional aspects in a more realistic environment. It also upgrades the knowledge on pharmacokinetics and pharmacodynamics of compounds. There is no doubt that HoC technology is a game changer that will revolutionize clinical research in the upcoming years. This review explains the evolution of OoC to HoC, their potential use and limitations. More emphasis has been given on the potential use of HoC in pharmacology. Conclusions Pharmaceutical companies, academic institutions and regulatory agencies should initiate a joint venture to launch and utilize the full potential of HoC technology as a next generation alternative to preclinical or disease modelling studies.Item 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, HKDextran 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.Item Nano-bio compatibility of PEGylated reduced graphene oxide on mesenchymal stem cells.(2D Materials, 2017-05) Syama, S; Aby, CP; Maekawa, T; Sakthikumar, D; Mohanan, PVGraphene, with its unique physico-chemical properties, has found widespread biomedical application. It is used as a carrier for drug or gene delivery, photothermal therapy, bioimaging, in antibacterial agents and for the development of biosensors. Besides this, graphene has the scope to be used for wound healing, tissue engineering and regenerative medicine. In the present study, polyethylene-glycol-(PEG)ylated reduced graphene oxide (PrGO) was synthesized, characterized, and its interaction with mouse bone marrow mesenchymal stem cells (MSCs) was studied. in vitro cytotoxicity and differentiation study showed PrGO neither induced toxicity nor impaired the differentiation potential of the stem cells. PrGO was effectively internalized by MSCs and distributed throughout the cytoplasm. None of the PrGO was seen in the nucleus. Although it seems to induce increased reactive oxygen species (ROS) production inside the cell, no change in cell proliferation or cellular function was observed. Hence it is recommended that the synthesized PrGO is applicable for tissue engineering, and can also be used as a substrate platform for stem cell culture and differentiation.