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dc.contributor.advisorWollenberg, Amanda C.
dc.contributor.advisorPuig, Montserrat
dc.contributor.authorNarisetty, Susmitha
dc.date.accessioned2019-04-06T14:39:19Z
dc.date.available2019-04-06T14:39:19Z
dc.date.issued2019
dc.identifier.urihttp://hdl.handle.net/10920/36743
dc.descriptionv, 40 p.en_US
dc.description.abstractThe liver is a fundamental organ that is responsible for metabolism and excretion of drugs and is therefore exposed to drug-induced liver injury (DILI). This study was conducted to understand DILI when exposed to Carbenicillin (CBN), Flucloxicillin (FLX) and Pazopanib (PZP) using in vitro and in vivo models; and to establish an in vitro HLA B*57:01 gene transfected cell line model to study idiosyncratic DILI. In the first part, DILI upon drug exposure was tested in vitro using Hep 1C1C7 cell line by looking at cell growth, morphology, percent cell viability and IC50 of cell growth inhibition, followed by measuring the expression of biomarker proteins Hmgb1, S100a9, Nrf2 and AKR1b10 in primary hepatocytes. In the second part, in vivo effects of FLX on liver injury were studied by measuring alanine aminotransferase (ALT) levels in FLX treated transgenic mouse serum. The results from in vitro work showed a concentration dependent DILI upon FLX and PZP treatment, demonstrated by reduction in cell count and percent cell viability. However, no change in the release of stress biomarkers was observed in drug treated primary hepatocytes. In the in vivo studies FLX treated and control mice showed no difference in the expression of ALT levels. The HLA B*57:01 gene transfected Hep 1C1C7 cell line did not express the gene of interest making it unsuitable to study HLA linked idiosyncratic DILI. The differences in the observations from in vitro and in vivo work of this project along with future directions are discussed in this Thesis.en_US
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen_US
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titleHLA Driven, Dose Dependence of Flucloxacillin, Pazopanib and Carbenicillin on Hepatotoxicityen_US
dc.typeThesisen_US
KCollege.Access.ContactIf you are not a current Kalamazoo College student, faculty, or staff member, email dspace@kzoo.edu to request access to this thesis.


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  • Biology Senior Individualized Projects [1520]
    This collection includes Senior Individualized Projects (SIP's) completed in the Biology Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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