Browsing by Author "Athira, SS"

Now showing 1 - 12 of 12
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    Bio-interactions and risks of engineered nanoparticles
    (Environmental Research., 2019-02) Prajitha, N; Athira, SS; Mohanan, PV
    Nano technological research offered uncountable opportunities for engineered nanoparticles (ENPs) in the field of biomedical, pharmaceutical, agricultural, cosmetics, textiles, automobiles and electronic industry. Large scale commercial production and use of nanoparticles with smaller size and characteristic physico-chemical properties enhance the possibility of amenable toxicity to the environment. Primary important species of the ecosystem like bacteria, algae, fishes and plants are at high risk with nanoparticle (NP) toxicity. ENP distributed in air, water and soil can directly affect the livelihood or even the existence of smaller organisms. In day-today life, human beings are getting exposed to thousands of NPs via dermal contact, inhalation or ingestion. Topical application of sunscreens and cosmetics containing ENPs has the potential to induce photo toxicity under ultra violet irradiation. ENP intentionally or non-intentionally enter into the body will affect the entire organ system and execute their toxicity even in reproduction and fetal developmental stages. Unfortunately the existing researches to evaluate the in vivo and in vitro toxic effects of ENPs are inefficient to give the exact nature and depth of toxicity. Hence an effort was made to discuss on the characteristics, classification, synthesis, applications and toxic potentials of various classes of commercially relevant ENPs along with a detailed review on currently available literatures.
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    Comprehensive biology of antipyretic pathways
    (Cytokine, 2019-04) Prajitha, N; Athira, SS; Mohanan, PV
    Pyrogens, the fever inducing substances accidently enter into a human body through contamination from medical or pharmaceutical products may create mild to severe complications including septicaemia and shocking syndromes. To avoid such drastic situations all the pharmaceuticals and medical devices are analysed for presence of pyrogens prior to their release into market. The entry of exogenous pyrogens like bacterial endotoxins induces the release of endogenous pyrogens or inflammatory cytokines that activate immune system to defend against these pathogens. Generation of heat is considered as one of the important defence mechanism of body achieved through receptor mediated interaction of endogenous pyrogens at the thermoregulatory centre of hypothalamus. However, uncontrolled fever and febrile reaction may cause lethal effects to the subject itself. So a well sophistically functioning antipyretic mechanism is necessary to achieve thermoregulation. The coordinated interaction of antipyretic cytokines and other mediators are active in human immune system which play a crucial role in maintaining thermal homeostasis. The multiple interacting antipyretic signals and their mechanism are the major subjects of this review.
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    Determination of the bioavailability of zinc oxide nanoparticles using ICP-AES and associated toxicity
    (Colloids and Surfaces B: Biointerfaces., 2020-01) Sudhakaran, S; Athira, SS; Suresh Babu, S; Varma, HK; Mohanan, PV
    Advancement in nanotechnology has brought abundant number of products and materials in multiple fields including biomedicine owing to their unique physico-chemical properties. This further necessitates toxicity assessment of nanoparticles (NPs) before they are employed for product fabrication, medicinal, environmental or industrial purposes. Zinc oxide nanoparticles (ZnONPs) belong to the category of metal oxide NPs and hold quite a lot of possibilities to be applied in aforementioned scenarios. Present study addresses the probable outcomes of bio-nano interaction of ZnONPs with healthy adult Wistar rats. Sphere head shaped ZnONPs were synthesized via wet chemical method. Physico-chemical characterization was performed using number of sophisticated techniques including HR-TEM, Zeta potential analysis, TGA and XRD. Size of the particles was found to be 43 nm and ensured homogenous distribution with high purity. For in vivo studies, as synthesized NPs were administered into rats via intravenous (i.v.) and intraperitoneal (i.p.) routes. Animals were sacrificed on 3rd, 14th and 21st day of exposure. Metabolically relevant tissues like brain, liver, kidneys and spleen were isolated and analyzed for different parameters like gross pathology, haematology, neurotoxicity, target organ toxicity, immunotoxicity etc. Results suggests that ZnONPs did not elicit significant toxic responses in rat except a few anomalies with histology, ion content and antioxidant system within liver; thereby confirming potent hepatotoxicity. Hence the study recommends adopting surface functionalization strategies for reducing toxic response of ZnONPs during various application rationales.
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    Dextran stabilized fullerene soot induced toxicity on alveolar epithelial cells (A549 cells)
    (Environmental Research., 2020-09) Athira, SS; Biby, ET; Mohanan, PV
    Fullerene comprises the major allotrope of carbon holding several fruitful potentials to be applied in various industrial and biomedical scenarios. Scientists have acquired large number of data on fullerene research using its derivatives like C60, C70 etc. Nevertheless, a precise focus on fullerene soot nanopaticles and its toxic impacts in living tissue is still behind mainstay even if it represents the crude parent form of all other derivatives. Present study addresses an acute toxicity profiling of fullerene soot nanoparticles in alveolar epithelial cells (A549) as a paradigm of pulmonary exposure. Surface functionalization was given for fullerene soot nanoparticles using dextran polymer as a mean to establish a stable homogenous dispersion (denoted as dFSNPs hereafter). Following functionalization, dFSNPs were characterized for various parameters including size, surface charge, morphology and functional groups using DLS, Zeta potential analysis, TEM and FT-IR measurements respectively. Effective dextran functionalization was evident from the characteristic peaks in FTIR spectra. Cell viability assessed using MTT and NRU assays; both of which showed a dose dependent cytotoxic response. Thymidine incorporation also confirmed similar trend in viability rate. In accordance with literatures, DCFHDA assay confirmed free radical scavenging activity of fullerene nanoparticles. An altered cellular morphology was observed under fluorescent microscope. Sub-cellular functionalities including lysosomal integrity and mitochondrial stability were found to be compromised at highest tested concentration of dFSNPs (160 μg/ml) without any genotoxic impacts within nuclear premises. FACS analysis following Annexin-PI staining confirmed apoptotic cell death. Hence the overall study substantiated dose dependent toxicity of dFSNPs which is likely to occur during pulmonary exposure.
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    Dextran stabilized fullerene soot induced toxicity on alveolar epithelial cells (A549 cells)
    (Environmental Research., 2020-05) Athira, SS; Biby, ET; Mohanan, PV
    Fullerene comprises the major allotrope of carbon holding several fruitful potentials to be applied in various industrial and biomedical scenarios. Scientists have acquired large number of data on fullerene research using its derivatives like C60, C70 etc. Nevertheless, a precise focus on fullerene soot nanopaticles and its toxic impacts in living tissue is still behind mainstay even if it represents the crude parent form of all other derivatives. Present study addresses an acute toxicity profiling of fullerene soot nanoparticles in alveolar epithelial cells (A549) as a paradigm of pulmonary exposure. Surface functionalization was given for fullerene soot nanoparticles using dextran polymer as a mean to establish a stable homogenous dispersion (denoted as dFSNPs hereafter). Following functionalization, dFSNPs were characterized for various parameters including size, surface charge, morphology and functional groups using DLS, Zeta potential analysis, TEM and FT-IR measurements respectively. Effective dextran functionalization was evident from the characteristic peaks in FTIR spectra. Cell viability assessed using MTT and NRU assays; both of which showed a dose dependent cytotoxic response. Thymidine incorporation also confirmed similar trend in viability rate. In accordance with literatures, DCFHDA assay confirmed free radical scavenging activity of fullerene nanoparticles. An altered cellular morphology was observed under fluorescent microscope. Sub-cellular functionalities including lysosomal integrity and mitochondrial stability were found to be compromised at highest tested concentration of dFSNPs (160 μg/ml) without any genotoxic impacts within nuclear premises. FACS analysis following Annexin-PI staining confirmed apoptotic cell death. Hence the overall study substantiated dose dependent toxicity of dFSNPs which is likely to occur during pulmonary exposure.
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    Effect of polymer functionalized fullerene soot on C6 glial cells
    (European Polymer Journal, 2020-03) Athira, SS; Biby, TE; Mohanan, PV
    Fullerene is crafting its dominance in various fields of science. Advanced exploration on the applicability of fullerene and the enhanced chances of exposure has prompted valuation of its biocompatibility. The antioxidant and radical scavenging characteristic of fullerene raises assurance for various biomedical applications. Nevertheless, the hydrophobicity of fullerene lowers its charm in healthcare applications where stable water dispersity is fundamental. In this study, one of the highly exposed forms of fullerenes; fullerene soot was subjected to in vitro toxicity evaluation. For nullify hydrophobic consistency, soot nanoparticles were surface functionalized with dextran polymer. Even though various tissue-specific toxicity evaluations of fullerene are been reported, the idea about its effect on the neuronal tissue still remains vague. In the context, the well-characterized dextran-coated fullerene soot (Dex-FS) nanoparticles were exposed to C6 glial cells to understand the cellular response of Dex-FS. Glial cells are present in plenty in the central nervous system (CNS) and provide support and insulation to neurons. Hence, glial cells turn out to be an ideal choice for in vitro CNS system. Dex-FS showed dose-dependent toxicity. The integrity of cytoskeleton was found to be compromised. Dex-FS was found to trigger ROS production in a dose and time dependent manner. The lysosomal activity and mitochondrial membrane potential during post Dex-FS treatment was evaluated using acridine orange and rhodamine-phalloidin staining. The molecular level toxicity was evaluated by DNA laddering and DAPI staining. The amount of live and dead cells after treating C6 glial cells with Dex-FS was estimated by Calcein AM/ PI flow cytometry. The neurotoxic impact of fullerene soot nanoparticles explored in the present study thus presents a debatable topic regarding vehicle exhaust which contains higher amounts of fullerene soot as active ingredient.
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    Fullerene C70: A Promising Carbon Cage for Biomedical Applications
    (Trends Biomater. Artif. Organs, 2021-03) Ashtami, J; Athira, SS; Mohanan, PV
    Nanomaterials have conquered the field of science and technology, and are considered as the driving force behind most of the scientific discoveries in the 20th century. Fullerenes entail one among the leading members of the family of nanomaterials which are characteristically allotropic forms of carbon. The uniqueness lies in its structure itself that it has a closely packed cage-like pattern of carbon atoms arranged like a ‘buckyball’. This peculiarity further makes the nanostructure a suitable platform for a wider range of medical and non-medical applications. Furthermore, proper fine-tuning or modification can accomplish targeted application requisite. Nevertheless, such an increased level of applications concurrently necessitates toxicity assessment as well. Available studies on the cytocompatibility of fullerene C70 confirm the fact that C70 is not eliciting any discernible toxic impacts in fibroblast cells up to the maximum tested concentration. This view undoubtedly justifies the utilization of fullerene C70 in various applications. However, authors recommend deeper toxicity evaluations to guarantee its biocompatibility and hence wider applicability.
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    Glial Cell Colony Injured on Exposure to Fullerene Soot Nanoparticles
    (Letters in Applied Nano Biosciences, 2020-12) Athira, SS; Ashtami, J; Mohanan, PV
    An expansion in the field of nanotechnology and their applications in medicine and pharmaceuticals have revolutionized the 20th century. Principally it deals with particles exhibiting a size below 100nm at least in a single dimension. Various fields that gain application potentials of nanotechnology include health and medicine, electronics, energy and environment, space research, etc. Advancements in experimental techniques have to lead to the development of multi functionalized nanoparticles like fullerenes, which is one of the allotropic forms of carbon. Fullerene was initially fabricated by laser ablation of graphite in an inert atmosphere. The crude early form consists of a mixture of interlocked carbon cages in its impure version, referred to as fullerene soot. Nature gets exposed to fullerene soot from a cluster of sources, including vehicle, industrial, and other household exhausts. An increasing level of exposure requires toxicity evaluation of such materials in biological systems. Present study addresses in vitro toxicity studies of fullerene soot nanoparticles in C6 glial cells. The study particularly analyzes cell viability assays, morphological evaluations, organelle functionality analysis, live-dead assays, and nuclear integrity measurement. The study confirms the dose-dependent toxicity of the nanomaterials, which further recommends proper precautions to be taken during exposure occasions
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    Interaction of nanoparticles with central nervous system and its consequences
    (American Journal of Research in Medical Sciences, 2018-09) Athira, SS; Prajitha, N; Mohanan, PV
    Nanotechnology has gained a non-replaceable role in a host of applications in biomedical, agricultural, consumer, military, and in industrial sectors. However, when observed through the perspective of the central nervous system (CNS) particularly, studies evidently provide data on both beneficial and detrimental effects of nanoparticles (NPs). While there exist a milieu of beneficial applications like axonal regeneration, CNS imaging, neurological surgeries etc., NPs open the doorway for an array of toxic reactions in CNS centers because of their effortless passage through brain barriers. Even though literature endow with generalized toxic mechanisms mediated by NPs in varying tissues, specific toxic reactions in CNS are still lacking. Present review mainly focuses on different routes through which NPs get access into the brain and certain modes of toxic mechanisms exhibited by NPs in CNS. A number of applications of NPs in the diagnosis and treatment of CNS disorders also will be reviewed in concise.
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    Nano Fullerene Mixture Impose Threat to Alveolar Epithelial Cells
    (Ec Pharmacology And Toxicology, 2020-08) Athira, SS; Ashtami, J; Mohanan, PV
    Fullerenes, the symmetric allotrope of carbon with bucky ball structure is gaining high magnitude of interest in material chemistry as well as in medical scheme. Fullerenes find its role in batteries, solar cells, for hydrogen storage, trapping reactive species, as lubricants, MRI contrast agents, protective coatings, superconductors and also in biomedical applications as neuroprotective agents, anti-oxidant, enzyme inhibitor, delivery vector, biosensor, for photodynamic therapy etc. Apart from the intentional exposure during usage in various applications, nano fullerene mixture is present in automobile/industrial exhaust, release from incomplete combustion of fossil fuels etc. Increased exposure entail the exigency for toxicity profiling of fullerene. Inhalation being a major route of nanoparticle exposure compels lungs at high risk of toxicity due to accumulation. Retention at the “alveoli site” potentially causes translocation into blood that further complicates the scenario. Improved perception on the effect of nano fullerene mixture on lung cells is needed to make a critical inference.
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    Pyrogens, a polypeptide produces fever by metabolic changes in hypothalamus: Mechanisms and detections.
    (Immunology Letters, 2019-01) Prajitha, N; Athira, SS; Mohanan, PV
    Fever is one of the cardinal symptoms of onset of an infection or inflammation and is the common clinical indicator for medical consultation in mammalian host worldwide. Simply, fever manifested with elevation of body temperature from normal physiological range represents adaptive response of immune system on challenge with an infectious and non-infectious circumstance. Fever usually initiated in the periphery as a result of interaction of immune cells with exogenous or endogenous pyrogens. Peripheral pyrogenic signals gain access to the central nervous system via humoral and neural route. Humoral pathway was initiated with production of pyrogenic cytokines and prostaglandins from immune cells of blood as well as liver, transmitted directly to pre-optic area of hypothalamus through the circumventricular organ of brain. On the other hand an alternative pathway was initiated by the same cytokines indirectly via stimulating the vagal sensory neurons result in pyrogenic fever; so-called neuronal pathway. If the magnitude of pyrogens associated fever is very high, it will lead to severe illness ranging from septic shock to death. So it is necessary to evaluate the presence of pyrogens in implants, medical devices, drugs and biological materials to ensure safety in biomedical applications and therapeutics. Classification, route of administration, mechanism of action and detection of pyrogens and associated products are the major subject of this review.
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    Zinc oxide nanoparticle induced neurotoxic potential upon interaction with primary astrocytes
    (Neurotoxicology, 2019-07) Sudhakaran, S; Athira, SS; Mohanan, PV
    As obvious from the basic prerequisite of any particle in nanoscale, Zinc oxide nanoparticles (ZnO NPs) possess numerous tunable properties distinct from their bulk formulations. Emerging innovations in various sectors of nanotechnology are exploiting ZnO NPs largely. This inturn picks up the occasions of human exposure irrespective of the application fields. Although the platform of nanotoxicology has been garnished with nano-bio interaction studies using different cell lines, a few are existing so far comprising primary cells which symbolize realistic in vivo environment. The present study addresses the neurotoxic potential of ZnO NPs using primary astrocytes isolated from post-natal 0–2 day old rat pups. Cells were cultured and maintained in DMEM F12 followed by purification. ZnO NPs generated by wet chemical method was then characterized both physico chemically and biologically. All of the techniques confirmed homogenous distribution of NPs and ensured enough colloidal stability. Bio-nano interaction studies commence on cell viability assays (MTT and NRU) and both of which confirmed dose and time dependent cytotoxicity. Alterations within cellular morphology, cytoskeletal arrangement, lysosomal stability, mitochondrial membrane potential (MMP) and caspase activation were evaluated by standardized techniques. All of the assays substantiated significant toxic consequences in astrocytes with characteristic hall marks. Apoptotic cell death was noted without any deformations of nuclear material. A comparative toxicity study using ZnO NPs, ZnCl2 and ZnO bulk form was performed which confirmed nanospecific toxicity of ZnO NPs. Overall study evidently provide cautious information that ZnO NPs is capable of eliciting serious neuronal tissue damages which can turn out to be fatal during prolonged exposure.