A Protective Function Against Radical Stress Mediated by the Intracellular Calcium in Rat Hepatocytes

Abstract

The role of intracellular Ca²⁺ in CCl₄ hepatotoxicity in rats was clarified by measuring detailed changes in serum ALT values and intracellular Ca²⁺ after CCl₄ administration. Intracellular Ca²⁺ responded to CCl₄ intoxication with a biphasic increase. The first intracellular Ca²⁺ peak increased up to 5.6-fold the control level at 1 hour, and the second Ca²⁺ peak 6.5-fold at 3.5 days. We further examined the effects of drugs on serum ALT activity and intracellular Ca²⁺ in rats administered at 1 hour prior to or 3 hours after CCl₄ administration. The results showed that the first Ca²⁺ increase might be attributable to a signal arising from the extent of hepatic injury. The second Ca²⁺ increase might act to activate cellular protective functions. We discussed that sustained intracellular Ca²⁺ increases may be involved in autoprotection, namely susceptibility against a toxication.