Figure 4
– Animal weights and copper delivery at 15 days. Treatment began at day 4. CuATSM has a backbone methyl group at R1 and at R2, CuPTSM has one methyl and one hydrogen, and CuGTSM has a hydrogen at R1 and at R2.
Talk about importance of bond length, electron density, reduction potential.
No treatment group weighed significantly more or less than untreated, though CuATSM-treated animals weighed significantly more than CuGTSM-treated animals
[ANOVA, F(3, 34) = 4.333, p=0.0109, Tukey post-hoc][JM14] .Measurements of COX activity reflect a significant effect of CuATSM- and CuPTSM treatment [ANOVA, F(3, 30) = 12.48, p < 0.0001, Tukey post-hoc]. Meanwhile, CuGTSM-treated animals were not significantly different from untreated, and no treated group was significantly different from another regarding COX activity. Treatment with CuATSM or CuPTSM had a significant effect on accumulation of mature SOD, but the data for CuGTSM, despite trending similarly to CuATSM and CuPTSM, were too disperse to draw statistical significance from [ANOVA, F(3, 19) = 4.682, p = 0.0130, Tukey post-hoc].
Given that the early development crisis is seemingly caused by a copper-dependent COX deficiency in the CNS, we hypothesized that all Cu(II)-bisthiosemicarbazones capable of restoring COX activity in the CNS would rescue the early death seen in SODWTxCCS mice. However, our results here suggest there is more to rescuing the early crisis than simply delivering copper to the CNS.
To investigate the possibility that the bisthiosemicarbazone ligand molecules themselves (without copper) have differential, possibly toxic, effects, we
treated[JM15] nontransgenic mice with ATSM, PTSM, or GTSM free ligands from 4-21 days and recorded animal weights (Figure 5). GTSM- and PTSM-treated animals weighed significantly less than ATSM- and control-treated animals [ANOVA, F = 48.68, p < 0.0001, Tukey post-hoc].