Figure 5.

Micrographs of hematoxylin/eosin stained liver sections as a function of treatment as described in Figure 3. Like cardiac tissue sections, the hepatic tissue sections of the control mice demonstrated a healthy appearance. Low magnification (top panel) revealed well formed cords of hepatocytes, separated by well defined sinusoids. At higher magnification (lower panel), the hepatocytes stained in a fairly uniformly distributed punktate-like pattern. A similar pattern was seen for livers from mice treated with 2.5 mg/kg Dox. Little significant difference was noted between Dox and control livers, with the former lacking the periportal hepatocyte damage and disorganization that has been described at higher dosages. Treatment of mice with PPD, however, did induce some evidence of hepatotoxicity. A dose-dependent decrease in the uniformity of the punktate staining pattern likely indicates a cytoplasmic buildup of lipid deposits, a possible result of lipid peroxidation by the Dox and Doxaz resulting from prodrug activation. Low magnifications indicated a progression in the severity of damage, from most significant in the periportal regions (P) and decreasing slightly towards the central vein (C) of the classical lobule. The bars in the upper panels represent 100 µm and those in the lower panels show 25 µm.