Effects of feeding and fasting on hepatolobular distribution of glutathione and cadmium-induced hepatotoxicity.

Relationship between hepatolobular distribution profile of glutathione (GSH) and cadmium (Cd)-induced hepatotoxicity was examined in both fed and fasted rats by computerized densitometry of histochemically stained GSH in the liver sections using an image analyzer system. In fed rats, density gradient distribution of hepatolobular GSH, which was higher in the periportal region than in the perivenous one, was always observed even at a diurnally minimal concentration of GSH. This heterogeneous distribution of GSH, however, disappeared in fasted rats, even though the hepatic GSH concentration recovered to 81% of the control level in rats fasted for 48 h. In histopathological examination on livers 24 h after oral treatment of fed and fasted rats with 60 mg Cd/kg, zonal necrotic changes were observed from the perivenous to midlobular region but not in the periportal one in fed rats even at a diurnally minimal concentration of hepatic GSH. On the other hand, necrotic changes in the liver extended to the panlobular region including the periportal one in fasted rats. These necrotic changes were greater with a longer duration of fasting. These results suggest that the density gradient distribution of hepatic GSH but not the actual concentration of the compound plays an important role in protecting rats against acute hepatotoxicity of Cd.