Theses And Dissertation

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    Assessment of antioxidant potential of phytochemicals in human glioblastoma (U-87 MG) cells
    (Central University of Punjab, 2014) Kaur, Manpreet; Mantha, Anil K.
    Imbalance between production of reactive oxygen/nitrogen species (ROS/RNS) leads to oxidative stress and has been well documented for mitochondrial dysfunction, a prime cause towards pathogenesis of neurological diseases and cancer. Glioblastoma Multiforme (GBM) is a highly aggressive, invasive and primary brain tumor which shows resistance to chemotherapy and radiotherapy. Superoxide dismutase (SOD) is an antioxidant enzyme that scavenges the production of superoxide radicals and dismutases into H?O? which is further converted into H?O and O? by catalase (CAT) enzyme. Apurinic/Apyrimidinic endonuclease (APE1) is a central enzyme of base excision repair (BER) pathway with two important functions; DNA repair and redox regulation of transcription factors (TFs) responsible for cell survival. In this study, it was seen that oxidative stress induced by endogenously found oxidants H?O? and glucose oxidase (GO) enhanced the activities of both CuZn-SOD and MnSOD in U-87 MG cells. In addition, CuZn-SOD levels were found to be increased in H?O?-induced oxidative stress and MnSOD levels were found to be increased in both H?O? and GO- induced oxidative stress. Further, pretreatment with phytochemicals Curcumin and Quercetin modulated the activities and expression of both forms of SOD studied. The BER-pathway enzyme, APE1 level was found to be decreased in mitochondria of oxidative stress induced U-87 MG cells by H?O? and GO, and in contrast APE1 level was found to be increased in cytosol, which indicates that oxidative stress affects the expression level and sub-cellular localization of APE1. Taken together, these results indicate that in GBM it is more likely that activated SOD a key player of antioxidant system and APE1 a key player in BER-pathway might be facilitating cancer cells to survive in oxidative stress environment.
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    Assessment of Extract of Syzygium cumini Against Doxorubicin Induced Cardiotoxicity
    (Central University of Punjab, 2018) Chayan, Mukherjee; Monisha Dhiman
    For the past four decades, doxorubicin (DOX) has been used to treat cancer, mainly solid tumours and haematological malignancies. However, clinical community is greatly concerned regarding the administration of this as DOX treatment is commonly associated with dose-dependent cardiotoxicity. Attempts at alleviating drug generated cardiac damage using an extract from different parts of plants with radical scavenging property are a promising area of research. Hydroalcoholic extract derived from fruit pulp of Syzygiumcumini which has a significant antiradical scavenging effect. This study aims to assess the effect of parallel administration of SC fruit pulp extract (SC) on mitigating or preventing DOX induced cardiotoxicity in vitro using H9c2 cardiomyoblast cell lines. Addition of SC fruit pulp extract and DOX were performed for both treatment and control sets on H9c2 cells. SC fruit pulp extract showed strong ABTS cation radical scavenging activity in a dose dependent manner. MTT assay was used to study the cytotoxic effect of SC fruit pulp extract and DOX. ROS levels were estimated using NBT assay and DHE assay. The results showed that DOX has significant cytotoxic effect in a dose dependent manner while SC fruit pulp extract did not display any significant cytotoxicity on H9c2 cells. The DOX induced ROS production was found to be significantly reduced in SC fruit pulp extract treated cells. Results of the current study also suggest that the treatment of SC fruit pulp extract along with DOX, displayed cardioprotective potential in H9c2 cells by: 1) reducing lipid peroxidation; 2) decreasing extracellular nitric oxide (NO); 3) decreasing the expression of the protein p47phox and iNOS/NOS-2. These results clearly suggest that treatment of SC fruit pulp extract along with DOX reduces the DOX induced toxicity and hence can be a promising therapeutic intervention in managing DOX mediated cardiotoxicity.
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    Oxidative stress responses to sub-lethal dose of Cry toxin in the larvae of castor semilooper, Achaea janata
    (Central University of Punjab, 2018) Singh, Kanika; Chaitanya,R.K.
    Development of synthetic insecticides to reduce the level of infestation led to deleterious effects on environment and human health. This lead to the development of ecofriendly pest management alternatives including Bacillus thuringensis (Bt). Bt produce Crystal (Cry), Cytotoxic (Cyt) and Vegetative (Vip) proteins with insecticidal activity against different orders of lepidoptera. Of late, pest resistance against Bt is reported in countries.The reduced toxicity of Bt formulation from degradation by UV light, wash-off by rain, drying, temperature, and soil acidity as well as its chemistry. Further, insects sense pesticides through odorant receptors and move away quickly, there is always a possibility of a population of larvae to get exposed to sub-lethal doses of toxin which might exhibit variable effects and escape mortality and eventually generate resistance. Sub-lethal dose lead to the generation of oxidative stress in the insect and eventually scavenged by anti-oxidant enzymes. These stress responses would enhance our understanding of adaptations for survival and resistance development. The current study is an attempt to monitor the antioxidative responses at the transcriptional level upon sub-lethal exposure of Cry toxin in the larvae of an polyphagous pest castor semilooper, Achaea janata. prevalent in the Indian subcontinent.