Figure 5. Pharmacotoxicity of 1R-Chl and 1S-Chl in mice.

(A) After single I.V. bolus injection of 1R-Chl at 2.25, 22.5, or 225 mg/kg, and PBS into Balb/c mice, the mice were subjected to gross anatomical observation followed by detailed histological analysis (Left). Mice were also injected with 1R-Chl with the indicated dose (0.75, 7.5, and 75 mg/kg) three times in one week. Half of the experimental population was euthanized after 24 h, and the other half after 7 days (as indicated). Animals were subjected to gross behavioral and anatomical observation followed by a detailed histological analysis (Right). (B) Toxic doses of 1R-Chl can cause microvacuolar hepatopathy. Mice were subjected to the toxicity studies, including injections of a dose-regime ten times higher than the therapeutic dose-regime. Representative tissues, including liver, were fixed in 10% formalin, trimmed for histology, embedded in paraffin, 3.0 micron sections were cut, mounted on glass slides and stained with H&E. Photomicrographs of H&E sections from liver of animals that received PBS and euthanized 7 days post-treatments (control), 3×75 mg/kg and euthanized 24 h post-treatment, and 3×75 mg/kg and euthanized 7 days post-treatments were shown (indicated above each picture). Morphology of the section is indicated below each picture.