We have recently reported that transferrin (Tf)-unbound gallium-67 (
67Ga) may be taken up into the liver of carbon tetrachloride (CCl
4)-treated rats. In the present study, we attempted to clarify detailed mechanism of Tf-unbound
67Ga uptake by hepatocytes treated with CCl
4 using
in vitro experimental system. Hepatotoxic damages by CCl
4 are mostly attributed to radical formed by an action of cytochrome P450. P450 isozymes have a higher expression in the perivenous hepatocytes (PVH) more than periportal hepatocytes (PPH). Therefore, we thought that the uptake of
67Ga which had been used for the detection of liver damage might have a zonal difference. The results of ALT activities showed that the CCl
4 exposure for 4 h strongly impaired PVH more than PPH. The uptake of
67Ga by PVH treated with CCl
4 was also higher than that by PPH. Moreover, the uptake of
45Ca by PVH was higher than that by PPH. In order to investigate whether
67Ga passed through calcium channel of hepatocytes, we made use of calcium channel blocker and activator. The Ca
2+-channel blocker, verapamil, significantly decreased the uptakes of
45Ca and
67Ga by PPH and PVH pretreated with CCl
4. The addition of the Ca
2+-channel activator, Bay K8644, significantly increased the uptake both of
45Ca and
67Ga by PPH pretreated with CCl
4. In the present study, it was demonstrated that the uptake of Tf-unbound
67Ga preferentially occurred in CCl
4-damaged PVH and
67Ga was taken up into the hepatocytes in part through calcium channel.
View full abstract