HLA Driven, Dose Dependence of Flucloxicillin, Pazopanib and Carbenicllin on Hepatotoxicity
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Authors
Narisetty, Susmitha
Issue Date
2019
Type
Presentation
Language
en_US
Keywords
Alternative Title
Abstract
The 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.
1) 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.
2) 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 work.
Description
1 Broadside. 48"W x 36"H
Citation
Publisher
Kalamazoo, Mich. : Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.