Vesicular delivery of biologically active compounds for combating hepatocellular mitochondrial oxidative damage

ThakurChoudhury, Somsubhra (2017) Vesicular delivery of biologically active compounds for combating hepatocellular mitochondrial oxidative damage. PhD thesis, CU.

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    Supervisors

    SupervisorsEmail
    Ali, Nahid

    Abstract

    Liver, the largest organ in our body, metabolizes different chemicals and xenobiotic substances like drugs, carcinogens etc. that enter into the body and therefore become prone to these chemical mediated oxidative damage. According to World Health Organization (WHO), right now there are around 5.5 million chronic liver disease patients now in USA and if considered globally the number is much bigger. Different xenobiotic materials that cause serious health hazards are alcohol, carbon tetrachloride (CCl4), aspirin, arsenic, diethylnitrosamine (DEN) etc. Since human liver metabolizes CCl4 in a manner similar to that of rodents, CCl4 induced liver injury can be an appropriate model for chemical induced liver injury study. Short term administration of CCl4 causes hepatic injury, centrolobular necrosis, steatosis and inflammation. Oxidative stress is a principal aspect of hepatic damage. The mitochondrion is the bioenergetic and metabolic center of eukaryotic cells. Mitochondrion is the target as well as the source of ROS generated through CCl4 administration. Our studies showed that apart from the formation of mitochondrial ROS CCl4 also damages mitochondria and triggers mitochondria mediated apoptotic pathway. Curcumin, although has anti-oxidative, anti-carcinogenic, anti-inflammatory and immunomodulatory properties, but its low aqueous solubility and poor gastrointestinal absorption has limited its therapeutic application. Our study demonstrated that both liposomal and nanoparticulated formulation can increase the bioavailability of free curcumin, still nanoparticulated formulation has a relative bioavailability four times higher than liposomal formulation. It was also found that both liposomal as well as nanoparticulated formulations can increase the efficacy of curcumin many folds. However, due to its small size, better cellular absorption and longer persistence in the circulating system, curcumin loaded nanoparticles showed better protection from oxidative stress, mitochondrial damage and disruption from cellular architecture and thus can be considered as a promising therapeutic strategy against liver toxicity.

    Item Type: Thesis (PhD)
    URI: http://www.eprints.iicb.res.in/id/eprint/2631
    Subjects: Infectious Diseases and Immunology
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 01 May 2017 11:20
    Last Modified: 15 Jun 2018 17:39
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