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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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