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    Mar 2014
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Identification of Adverse Outcome Pathways for the Nephrotoxicity of Nucleoside and Nucleotide Anti-Viral Drugs

pdf fileBenz RD; Cayley A; Drewe WC; Kruhlak NL; Surfraz B;

We report the construction of AOPs to describe the mechanisms of the in vivo nephrotoxicity of anti-viral drugs. Structurally related nucleoside and nucleotide drugs lead to histologically and biochemically proven structural and functional alterations of both proximal tubular and glomerular cells. Mitochondrial toxicity has been implicated in these highly metabolically active renal cells as one potential MIE, which is likely to be related to the clinical mode of action of these compounds in vivo. Furthermore, these compounds can act as potent inhibitors of mitochondrial polymerase gamma, which leads to mitochondrial toxicity.

Presented by William Drewe at SOT, Phoenix, USA; 27th March 2014.

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