Article: PDF OnlyLondon Erwin J.; Naukam, Rebecca J.; Sastry, B. V. RamaJournal of Cardiovascular Pharmacology: 1987 - p S77-S84 Free Abstract Summary Carbon tetrachloride, thioacetamide, and other hepatotoxic agents were each administered to rats in a single toxic dose. Experimental studies were designed to test the following hypothesis. The cell injury caused by some hepatotoxic agents is associated with the entry of calcium into the liver cells. Some calcium channel blocking agents, such as nitrendipine, will reduce both the entry of calcium and the associated liver-cell injury. In the following studies the hepatotoxic agents caused a rise in liver-cell calcium content that was associated in its time course with the development of contrilobular necrosis. Nitrendipine, and several other calcium channel blocking agents that were tested, reduced both the calcium increase and the centrilobular necrosis. The in-vivo experimental evidence suggests that this calcium increase is not solely the consequence of a calcium influx that follows cell necrosis. The ratio of the increase in calcium to-cell necrosis varied with the specific group of hepatotoxic agents employed. With some toxic compounds the calcium channel blocking agents diminished the calcium increase, but virtually eliminated the cell necrosis. The corollary is that a part of the calcium increase precedes the necrosis and may play a role in the development of cell injury. Acute and chronic ingestion of ethanol was not associated with an increase in liver-cell calcium content. Possible mechanisms and potential limitations of the observed protection from cell injury are discussed. These findings support the existing evidence that calcium channel blocking agents employed in treatment of cardiovascular disease may reduce the associated cell injury. © Lippincott-Raven Publishers.