• The Korean Journal of Pharmacology
• /
• v.32 no.1
• /
• pp.75-82
• /
• 1996

The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.