A Cytoprotection of Rat Hepatocytes Mediated by the Intracellular Calcium

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. Serum ALT activity clearly increased up to a peak value at 1 day after i.p. administration of CCl₄ at 0.2 ml/kg, and then decreased to the control level after 3 days. 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. 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⁺ and S100A4 increases may be involved in autoprotection or adaptive cytoprotection, namely susceptibility against a toxication.