Fig 6.

(A) (S)-2 is well tolerated in normal CD-1 mice which have been used as the model for acute toxicity experiments. Animals were injected i.p. only once with increasing (S)-2 concentrations dissolved in 0.1 ml DMSO and sacrificed after a week (S3). Pictures (magnification: ×200) reported in this panel concern the histopathology of organs explanted from mice which were treated with the higher drug dosage, i.e. 150 mg/kg, corresponding to about 5 mg/mouse. No specific drug-induced tissue alteration in treated versus mice treated with the vehicle alone was observed. Consecutive 2.5–5 μm sections of samples were stained with May-Grünwald/Giemsa and examined under a bright field microscope (Nikon Eclipse, mod. 50i) equipped with a digital camera (DS-5M USB2; Nikon Instruments, Florence, Italy). (B) Binding experiments in tissue extracts. The affinity of novel HDACi, at the two concentrations used (10 and 100 μM, respectively) for CBR was assayed by using membranes from rat cerebral cortex that were prepared as described by Mehta and Shank [17], while for PBR, rat kidney mitochondrial membrane preparations as described by Miccoli et al. were employed [18]. Bars were the means ± SE of three separate experiments; for details see S4.