Abstract #2957
31P MRS Assessment of Hepatic Mitochondrial Toxicity in Rat
Hasan Alsaid 1 , Mary V Rambo 1 , Tinamarie Skedzielewski 1 , James R Armitage 2 , Jon J Lyon 2 , and Beat M Jucker 1
1
Preclinical & Translational Imaging, LAS,
PTS, GlaxoSmithKline, King of Prussia, PA, United
States,
2
Safety
Assessment Tox/Path/Investigative, PTS, GlaxoSmithKline,
Ware, Hertfordshire, United Kingdom
A clinically translatable 31P-MRS method was used to
assess the high energy metabolite profile after the
administration of GSK121A (50mg/kg or 25mg/kg), a known
mitochondrial respiratory chain inhibitor. The results
showed that liver ATP concentrations remained unchanged,
Pi and Pi/ATP ratio were increased significantly in the
GSK121A treated groups compared to vehicle, associated
with a higher blood lactate level which correlated with
the change in body temperature. While steady state ATP
levels appear to be normal, there could potentially be a
decrease in ATP synthesis associated with decreased body
temperature and increase in Pi. This method may be used
to assess drug effects on hepatic mitochondrial function
in patients.
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