The role of intracellular Ca
2+ in CCl
4 hepatotoxicity in rats was clarified by measuring detailed changes in serum ALT values and intracellular Ca
2+ after CCl
4 administration. Intracellular Ca
2+ responded to CCl
4 intoxication with a biphasic increase. The first intracellular Ca
2+ peak increased up to 5.6-fold the control level at 1 hour, and the second Ca
2+ peak 6.5-fold at 3.5 days. We further examined the effects of drugs on serum ALT activity and intracellular Ca
2+ in rats administered at 1 hour prior to or 3 hours after CCl
4 administration. The results showed that the first Ca
2+ increase might be attributable to a signal arising from the extent of hepatic injury. The second Ca
2+ increase might act to activate cellular protective functions. We discussed that sustained intracellular Ca
2+ increases may be involved in autoprotection, namely susceptibility against a toxication.
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