Figure 1.

Protective effects of dexrazoxane pre-treatment on daunorubicin-induced decreases in RyR2 gene expression in hearts from chronically treated rats. Abbreviations are: daunorubicin treated, dexrazoxane vehicle pre-treated rats, Daun (n=4); dexrazoxane pre-treated, daunorubicin treated rats, Daun+ICRF (n=4); dexrazoxane pre-treated, daunorubicin vehicle treated rats, ICRF (n=3); daunorubicin and dexrazoxane vehicle treated rats, Vehicle (n=5). (A) shows that the RyR2 probe is specific for the cardiac isoform only; none was detected in the liver fractions. The probe for GAPDH binds equally well to mRNA from liver or heart. Lane 5 shows both probes in the same hybridization reaction with cardiac mRNA. (B) is a representative composite autoradiograph made from a single gel of a RPA of cardiac tissue GAPDH and RyR2 mRNA. Daunorubicin treatment produced decreases in RyR2 mRNA (lanes 8–11). Dexrazoxane pre-treatment prevented daunorubicin-induced reductions in RyR2 mRNA (lanes 12–15). There was no change in RyR2 mRNA with dexrazoxane treatment alone (lanes 5–7). GAPDH was not significantly altered by treatment. (C) is a histogram of data obtained from densitometric scans of autoradiographs from the RPA analysis. Pre-treatment with dexrazoxane prevented the daunorubicin-induced decrease in RyR2/GAPDH mRNA ratio. Dexrazoxane alone had no effect on the RyR2-GAPDH mRNA ratio. Values are mean±s.e.mean, for per cent RyR2/GAPDH mRNA expressed in arbitrary units. Experiments were run in duplicate. ^*Different from control values; P<0.02.