Silymarin Effects on Intracellular Calcuim and Cytotoxicity: A Study in Perfused Rat Hepatocytes After Oxidative Stress Injury

Author： Farghali H. KAMENIKOVÁ L. Hynie S. KMONICKOVÁ E.

Publisher： Academic Press

ISSN： 1043-6618

Source： Pharmacological Research, Vol.41, Iss.2, 2000-02, pp. : 231-237

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

The re-emergence of silymarin as a natural remedy for diseases of the liver and biliary tract necessitates revaluation of the efficiency of this compound and its possible mode of action. The aim of this study was to investigate the potentials of silymarin on the amelioration of hepatic injuries. The possible mechanism(s) that contribute to the hepatoprotective effect of silymarin and the role played by intracellular calcium (Ca²⁺_i) was investigated using tert -butyl hydroperoxide (TBH) and d -galactosamine (d -Gal) intoxication in a model of the isolated immobilized and perfused hepatocytes. Silymarin decreased lactate dehydrogenase (LDH) leakage, increased oxygen consumption, 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 Ca²⁺_iin hepatocytes significantly to a value of more than 600 n m and silymarin pre-treatment reduced the TBH- induced rise in Ca²⁺_iand brought Ca²⁺_ilevel to below 300 n m. Silymarin did not affect LD leakage or urea synthesis in d-Gal-injured cells. 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 Ca²⁺_iplays a pivotal role in a protective effect.