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Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Organ-Specific Contribution Of P450 Enzymes To Bioactivation And Acute Respiratory Tract Toxicity Of Naphthalene, Nataliia Kovalchuk
Legacy Theses & Dissertations (2009 - 2024)
Naphthalene (NA) is an omnipresent air pollutant and respiratory toxicant and a possible human lung carcinogen. NA induces cytotoxicity in airways following bioactivation by CYP (P450) enzymes. The overall goal of this study was to examine the relative contributions of hepatic and pulmonary CYPs to bioactivation, disposition and NA-induced pneumotoxicity in vivo. Substantial differences in the expression and enzymatic activity of P450s occur in various organs in human populations, which could modify susceptibility to NA-induced airway damage. The central hypothesis for this study was that NA has the potential to cause lung toxicity in humans and that the metabolism of …
Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan
Study Of Protective Role Of Cytochrome P450s In Inflammatory Bowel Disease Using Cprlow Mouse Model, Xiaoyu Fan
Legacy Theses & Dissertations (2009 - 2024)
Glucocorticoids (GCs) are potent regulatory factors for inflammation. The synthesis of GCs involves several cytochrome P450 enzymes, such as mitochondrial CYP11A1, CYP11B1, and microsomal CYP21. Previous studies have indicated that the GCs, including those released from adrenal glands, and those synthesized in extra-adrenal tissues, such as intestine, exert inhibitory effects on inflammatory bowel disease (IBD). In a previous study using an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, the results suggested that the intestinal P450s had a protective role in DSS-induced acute colitis. In this study, using a hypomorphic CPR mouse model (Cprlow), which presents a global …
Preparation And Application Of Transgenic And Knockout Mouse Models For Studies On Cytochrome P450 Functions, Yuan Wei
Legacy Theses & Dissertations (2009 - 2024)
The overall objective of this dissertation is to study the in vivo function of microsomal cytochrome P450 monooxygenases (P450s), which metabolize numerous drugs, chemical carcinogens, environmental pollutants, as well as endogenous signaling molecules such as steroid hormones and eicosanoids. The major research tool of this study involves the development of transgenic and knockout mouse models. The specific aims are 1) to study the in vivo function of NADPH-cytochrome P450 reductase (CPR) and CPR-dependent enzymes using a mouse model with a reversible hypomorphic Cpr gene; 2) to study the in vivo function of CYP2A13 with a CYP2A13- transgenic model; and 3) …