Silymarin effects on intracellular calcium and cytotoxicity: A study in perfused rat hepatocytes after oxidative stress injury

The re-emergence of silymarin as a natural remedy for diseases of the liver and biliary tract necessitates revaluation of the efficiency of this compo und and its possible mode of action. The aim of this study was to investiga te the potentials of silymarin on the amelioration of hepatic injuries. The possible mechanism(s) that contribute to the hepatoprotective effect of si lymarin and the role played by intracellular calcium (Ca-i(2+)) was investi gated using tert-butyl hydroperoxide (TBH) and D-galactosamine (D-Gal) into xication in a model of the isolated immobilized and perfused hepatocytes. S ilymarin decreased lactate dehydrogenase (LDH) leakage, increased oxygen co nsumption, reduced the formation of lipid peroxides (malondialdehyde, MDA) in hepatocytes that were altered by TBH and increased urea synthesis in the perfusion medium. TBH treatment increased Ca-i(2+) in hepatocytes signific antly to a value of more than 600 nM and silymarin pre-treatment reduced th e TBH-induced rise in Ca-i(2+) and brought Ca-i(2+) level to below 300 nM. Silymarin did not affect LD leakage or urea synthesis in D-Gal-injured cell s. It is concluded that silymarin hepatoprotective effect under the present experimental conditions is due to the inhibition of lipid peroxidation and that the modulation of hepatocyte Ca-i(2+) plays a pivotal role in a prote ctive effect. (C) 2000 Academic Press.