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. Author manuscript; available in PMC: 2015 Jun 10.
Published in final edited form as: Sci Transl Med. 2014 Dec 10;6(266):266ra170. doi: 10.1126/scitranslmed.3010189

Fig 4. VIS protects against doxorubicin cardiotoxicity via inhibition of MDH2.

Fig 4

(A) Bergapten, a potent VIS derivative, with an alkyl linker that could be attached to a solid support (Compound 1). (B) Affinity chromatography using a bergapten-linked matrix and competitive elution with VIS. BGP, bergapten; DM, dimethyl sulfoxide. (C) Western blot of gel in (B) incubated with an anti-MDH2 antibody. (D) Viability was measured in HL-1 cardiomyocytes treated with doxorubicin and MDH2 inhibitors. (E) Rescue from doxorubicin-induced cardiotoxicity and death in zebrafish co-treated with MDH2 inhibitors.. MBD, mebendazole; T4, L-thyroxine. Data were collected over 5 independent experiments, with a total of 150 zebrafish larvae treated for each condition. (F) L-malic acid protects against doxorubicin-induced cardiotoxicity and death in a dose-dependent fashion. (G) The malate-aspartate shuttle inhibitor AOA protects against doxorubicin-induced cardiotoxicity and death in a dose-dependent fashion. AOA, aminooxyacetate. For panels (D)-(G), data were collected from a total of 150 zebrafish larvae treated for each condition, as measured over 5 independent experiments. % Viability and % Rescue are depicted as mean +/− standard error of the mean. * p< 0.05, ** p<0.01, and *** p<0.001 using a two-tailed Student’s T-test.